Exploring the Role of Lipid-Binding Proteins and Oxidative Stress in Neurodegenerative Disorders: A Focus on the Neuroprotective Effects of Nutraceutical Supplementation and Physical Exercise
Abstract
:1. Introduction
2. Lipid-Binding Proteins in Neurodegenerative Disorders
3. Apolipoprotein E (ApoE)
4. Fatty Acid Binding Proteins in Neurodegeneration
5. Cholesterol Synthesis and Metabolism in the CNS
6. Oxidative Stress and Lipid Peroxidation
7. Antioxidant Supplementation in Neurodegenerative Diseases
8. Neuroprotective Effects of Physical Activity
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Kao, Y.-C.; Ho, P.-C.; Tu, Y.-K.; Jou, I.-M.; Tsai, K.-J. Lipids and Alzheimer’s Disease. IJMS 2020, 21, 1505. [Google Scholar] [CrossRef] [PubMed]
- Corraliza-Gomez, M.; Sanchez, D.; Ganfornina, M.D. Lipid-Binding Proteins in Brain Health and Disease. Front. Neurol. 2019, 10, 1152. [Google Scholar] [CrossRef] [PubMed]
- Glatz, J.F.C. Lipids and Lipid Binding Proteins: A Perfect Match. Prostaglandins Leukot. Essent. Fat. Acids 2015, 93, 45–49. [Google Scholar] [CrossRef] [PubMed]
- Dey, M.; Gunn-Moore, F.J.; Platt, B.; Smith, T.K. Brain Region–Specific Lipid Alterations in the PLB4 HBACE1 Knock-in Mouse Model of Alzheimer’s Disease. Lipids Health Dis. 2020, 19, 201. [Google Scholar] [CrossRef]
- Losada-Barreiro, S.; Bravo-Díaz, C. Free Radicals and Polyphenols: The Redox Chemistry of Neurodegenerative Diseases. Eur. J. Med. Chem. 2017, 133, 379–402. [Google Scholar] [CrossRef]
- Salim, S. Oxidative Stress and the Central Nervous System. J. Pharmacol. Exp. Ther. 2017, 360, 201–205. [Google Scholar] [CrossRef] [Green Version]
- Kamat, P.K.; Kalani, A.; Rai, S.; Swarnkar, S.; Tota, S.; Nath, C.; Tyagi, N. Mechanism of Oxidative Stress and Synapse Dysfunction in the Pathogenesis of Alzheimer’s Disease: Understanding the Therapeutics Strategies. Mol. Neurobiol. 2016, 53, 648–661. [Google Scholar] [CrossRef] [Green Version]
- Su, L.-J.; Zhang, J.-H.; Gomez, H.; Murugan, R.; Hong, X.; Xu, D.; Jiang, F.; Peng, Z.-Y. Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis. Oxid. Med. Cell. Longev. 2019, 2019, 1–13. [Google Scholar] [CrossRef] [Green Version]
- Mahalakshmi, B.; Maurya, N.; Lee, S.-D.; Bharath Kumar, V. Possible Neuroprotective Mechanisms of Physical Exercise in Neurodegeneration. IJMS 2020, 21, 5895. [Google Scholar] [CrossRef]
- Franzoni, F.; Scarfò, G.; Guidotti, S.; Fusi, J.; Asomov, M.; Pruneti, C. Oxidative Stress and Cognitive Decline: The Neuroprotective Role of Natural Antioxidants. Front. Neurosci. 2021, 15, 729757. [Google Scholar] [CrossRef]
- Agirman, G.; Yu, K.B.; Hsiao, E.Y. Signaling Inflammation across the Gut-Brain Axis. Science 2021, 374, 1087–1092. [Google Scholar] [CrossRef] [PubMed]
- Montesinos, J.; Guardia-Laguarta, C.; Area-Gomez, E. The Fat Brain. Curr. Opin. Clin. Nutr. Metab. Care 2020, 23, 68–75. [Google Scholar] [CrossRef] [PubMed]
- Ramasamy, I. Recent Advances in Physiological Lipoprotein Metabolism. Clin. Chem. Lab. Med. (CCLM) 2014, 52, 1695–1727. [Google Scholar] [CrossRef] [PubMed]
- Mahley, R.W.; Innerarity, T.L.; Rall, S.C.; Weisgraber, K.H. Plasma Lipoproteins: Apolipoprotein Structure and Function. J. Lipid Res. 1984, 25, 1277–1294. [Google Scholar] [CrossRef]
- Liu, T.; Chen, J.-M.; Zhang, D.; Zhang, Q.; Peng, B.; Xu, L.; Tang, H. ApoPred: Identification of Apolipoproteins and Their Subfamilies With Multifarious Features. Front. Cell Dev. Biol. 2021, 8, 621144. [Google Scholar] [CrossRef]
- Button, E.B.; Boyce, G.K.; Wilkinson, A.; Stukas, S.; Hayat, A.; Fan, J.; Wadsworth, B.J.; Robert, J.; Martens, K.M.; Wellington, C.L. ApoA-I Deficiency Increases Cortical Amyloid Deposition, Cerebral Amyloid Angiopathy, Cortical and Hippocampal Astrogliosis, and Amyloid-Associated Astrocyte Reactivity in APP/PS1 Mice. Alz. Res. Ther. 2019, 11, 44. [Google Scholar] [CrossRef] [Green Version]
- Owen, J.B.; Sultana, R.; Aluise, C.D.; Erickson, M.A.; Price, T.O.; Bu, G.; Banks, W.A.; Butterfield, D.A. Oxidative Modification to LDL Receptor-Related Protein 1 in Hippocampus from Subjects with Alzheimer Disease: Implications for Aβ Accumulation in AD Brain. Free. Radic. Biol. Med. 2010, 49, 1798–1803. [Google Scholar] [CrossRef] [Green Version]
- Hu, Y.; Meuret, C.; Martinez, A.; Yassine, H.N.; Nedelkov, D. Distinct Patterns of Apolipoprotein C-I, C-II, and C-III Isoforms Are Associated with Markers of Alzheimer’s Disease. J. Lipid Res. 2021, 62, 100014. [Google Scholar] [CrossRef]
- Zandl-Lang, M.; Fanaee-Danesh, E.; Sun, Y.; Albrecher, N.M.; Gali, C.C.; Čančar, I.; Kober, A.; Tam-Amersdorfer, C.; Stracke, A.; Storck, S.M.; et al. Regulatory Effects of Simvastatin and ApoJ on APP Processing and Amyloid-β Clearance in Blood-Brain Barrier Endothelial Cells. Biochim. Biophys. Acta (BBA)-Mol. Cell. Biol. Lipids 2018, 1863, 40–60. [Google Scholar] [CrossRef] [Green Version]
- Yerbury, J.J.; Poon, S.; Meehan, S.; Thompson, B.; Kumita, J.R.; Dobson, C.M.; Wilson, M.R. The Extracellular Chaperone Clusterin Influences Amyloid Formation and Toxicity by Interacting with Prefibrillar Structures. FASEB J. 2007, 21, 2312–2322. [Google Scholar] [CrossRef]
- Dassati, S.; Waldner, A.; Schweigreiter, R. Apolipoprotein D Takes Center Stage in the Stress Response of the Aging and Degenerative Brain. Neurobiol. Aging 2014, 35, 1632–1642. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sanchez, D.; Bajo-Grañeras, R.; Del Caño-Espinel, M.; Garcia-Centeno, R.; Garcia-Mateo, N.; Pascua-Maestro, R.; Ganfornina, M.D. Aging without Apolipoprotein D: Molecular and Cellular Modifications in the Hippocampus and Cortex. Exp. Gerontol. 2015, 67, 19–47. [Google Scholar] [CrossRef] [PubMed]
- Bajo-Grañeras, R.; Ganfornina, M.D.; Martín-Tejedor, E.; Sanchez, D. Apolipoprotein D Mediates Autocrine Protection of Astrocytes and Controls Their Reactivity Level, Contributing to the Functional Maintenance of Paraquat-Challenged Dopaminergic Systems. Glia 2011, 59, 1551–1566. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- García-Mateo, N.; Pascua-Maestro, R.; Pérez-Castellanos, A.; Lillo, C.; Sanchez, D.; Ganfornina, M.D. Myelin Extracellular Leaflet Compaction Requires Apolipoprotein D Membrane Management to Optimize Lysosomal-Dependent Recycling and Glycocalyx Removal. Glia 2018, 66, 670–687. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ganfornina, M.D.; Do Carmo, S.; Martínez, E.; Tolivia, J.; Navarro, A.; Rassart, E.; Sanchez, D. ApoD, a Glia-Derived Apolipoprotein, Is Required for Peripheral Nerve Functional Integrity and a Timely Response to Injury: Glial ApoD in Nerve Function and Regeneration. Glia 2010, 58, 1320–1334. [Google Scholar] [CrossRef] [PubMed]
- Ohno, N.; Ikenaka, K. Axonal and Neuronal Degeneration in Myelin Diseases. Neurosci. Res. 2019, 139, 48–57. [Google Scholar] [CrossRef]
- del Caño-Espinel, M.; Acebes, J.R.; Sanchez, D.; Ganfornina, M.D. Lazarillo-Related Lipocalins Confer Long-Term Protection against Type I Spinocerebellar Ataxia Degeneration Contributing to Optimize Selective Autophagy. Mol. Neurodegener. 2015, 10, 11. [Google Scholar] [CrossRef] [Green Version]
- Sung, H.K.; Chan, Y.K.; Han, M.; Jahng, J.W.S.; Song, E.; Danielson, E.; Berger, T.; Mak, T.W.; Sweeney, G. Lipocalin-2 (NGAL) Attenuates Autophagy to Exacerbate Cardiac Apoptosis Induced by Myocardial Ischemia: Lipocalin-2, autophagy and cell death. J. Cell. Physiol. 2017, 232, 2125–2134. [Google Scholar] [CrossRef]
- Kim, J.-H.; Ko, P.-W.; Lee, H.-W.; Jeong, J.-Y.; Lee, M.-G.; Kim, J.-H.; Lee, W.-H.; Yu, R.; Oh, W.-J.; Suk, K. Astrocyte-Derived Lipocalin-2 Mediates Hippocampal Damage and Cognitive Deficits in Experimental Models of Vascular Dementia: KIM et Al. Glia 2017, 65, 1471–1490. [Google Scholar] [CrossRef]
- Wan, T.; Zhu, W.; Zhao, Y.; Zhang, X.; Ye, R.; Zuo, M.; Xu, P.; Huang, Z.; Zhang, C.; Xie, Y.; et al. Astrocytic Phagocytosis Contributes to Demyelination after Focal Cortical Ischemia in Mice. Nat. Commun. 2022, 13, 1134. [Google Scholar] [CrossRef]
- Al Nimer, F.; Elliott, C.; Bergman, J.; Khademi, M.; Dring, A.M.; Aeinehband, S.; Bergenheim, T.; Romme Christensen, J.; Sellebjerg, F.; Svenningsson, A.; et al. Lipocalin-2 Is Increased in Progressive Multiple Sclerosis and Inhibits Remyelination. Neurol. Neuroimmunol. Neuroinflam. 2016, 3, e191. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yamazaki, Y.; Zhao, N.; Caulfield, T.R.; Liu, C.-C.; Bu, G. Apolipoprotein E and Alzheimer Disease: Pathobiology and Targeting Strategies. Nat. Rev. Neurol. 2019, 15, 501–518. [Google Scholar] [CrossRef] [PubMed]
- Martínez-Martínez, A.B.; Torres-Perez, E.; Devanney, N.; Del Moral, R.; Johnson, L.A.; Arbones-Mainar, J.M. Beyond the CNS: The Many Peripheral Roles of APOE. Neurobiol. Dis. 2020, 138, 104809. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Chen, K.; Sloan, S.A.; Bennett, M.L.; Scholze, A.R.; O’Keeffe, S.; Phatnani, H.P.; Guarnieri, P.; Caneda, C.; Ruderisch, N.; et al. An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex. J. Neurosci. 2014, 34, 11929–11947. [Google Scholar] [CrossRef] [Green Version]
- Chernick, D.; Ortiz-Valle, S.; Jeong, A.; Qu, W.; Li, L. Peripheral versus Central Nervous System APOE in Alzheimer’s Disease: Interplay across the Blood-Brain Barrier. Neurosci. Lett. 2019, 708, 134306. [Google Scholar] [CrossRef]
- Huang, Y.; Mahley, R.W. Apolipoprotein E: Structure and Function in Lipid Metabolism, Neurobiology, and Alzheimer’s Diseases. Neurobiol. Dis. 2014, 72, 3–12. [Google Scholar] [CrossRef] [Green Version]
- Raffaï, R.L.; Hasty, A.H.; Wang, Y.; Mettler, S.E.; Sanan, D.A.; Linton, M.F.; Fazio, S.; Weisgraber, K.H. Hepatocyte-Derived ApoE Is More Effective than Non-Hepatocyte-Derived ApoE in Remnant Lipoprotein Clearance. J. Biol. Chem. 2003, 278, 11670–11675. [Google Scholar] [CrossRef] [Green Version]
- Getz, G.S.; Reardon, C.A. Apoprotein E as a Lipid Transport and Signaling Protein in the Blood, Liver, and Artery Wall. J. Lipid Res. 2009, 50, S156–S161. [Google Scholar] [CrossRef] [Green Version]
- de Chaves, E.P.; Narayanaswami, V.; Christoffersen, C.; Nielsen, L.B. Apolipoprotein E and Cholesterol in Aging and Disease in the Brain. Future Lipidol. 2008, 3, 505–530. [Google Scholar] [CrossRef] [Green Version]
- Linton, M.F.; Gish, R.; Hubl, S.T.; Bütler, E.; Esquivel, C.; Bry, W.I.; Boyles, J.K.; Wardell, M.R.; Young, S.G. Phenotypes of Apolipoprotein B and Apolipoprotein E after Liver Transplantation. J. Clin. Investig. 1991, 88, 270–281. [Google Scholar] [CrossRef]
- Emi, M. Genotyping and Sequence Analysis of Apolipoprotein E Isoforms*1. Genomics 1988, 3, 373–379. [Google Scholar] [CrossRef]
- Kanekiyo, T.; Xu, H.; Bu, G. ApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners? Neuron 2014, 81, 740–754. [Google Scholar] [CrossRef] [Green Version]
- Neu, S.C.; Pa, J.; Kukull, W.; Beekly, D.; Kuzma, A.; Gangadharan, P.; Wang, L.-S.; Romero, K.; Arneric, S.P.; Redolfi, A.; et al. Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-Analysis. JAMA Neurol. 2017, 74, 1178. [Google Scholar] [CrossRef] [PubMed]
- Huang, Y.-W.A.; Zhou, B.; Wernig, M.; Südhof, T.C. ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Aβ Secretion. Cell 2017, 168, 427–441.e21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Piccarducci, R.; Daniele, S.; Polini, B.; Carpi, S.; Chico, L.; Fusi, J.; Baldacci, F.; Siciliano, G.; Bonuccelli, U.; Nieri, P.; et al. Apolipoprotein E Polymorphism and Oxidative Stress in Human Peripheral Blood Cells: Can Physical Activity Reactivate the Proteasome System through Epigenetic Mechanisms? Oxidative Med. Cell. Longev. 2021, 2021, 1–16. [Google Scholar] [CrossRef] [PubMed]
- Fleisher, A. Sex, Apolipoprotein E Ε4 Status, and Hippocampal Volume in Mild Cognitive Impairment. Arch. Neurol. 2005, 62, 953. [Google Scholar] [CrossRef] [Green Version]
- Caselli, R.J.; Reiman, E.M.; Locke, D.E.C.; Hutton, M.L.; Hentz, J.G.; Hoffman-Snyder, C.; Woodruff, B.K.; Alexander, G.E.; Osborne, D. Cognitive Domain Decline in Healthy Apolipoprotein E Ε4 Homozygotes Before the Diagnosis of Mild Cognitive Impairment. Arch. Neurol. 2007, 64, 1306. [Google Scholar] [CrossRef] [Green Version]
- Li, W.; Qiu, Q.; Sun, L.; Li, X.; Xiao, S. Short-Term Adverse Effects of the Apolipoprotein E Ε4 Allele over Language Function and Executive Function in Healthy Older Adults. NDT 2019, 15, 1855–1861. [Google Scholar] [CrossRef] [Green Version]
- Tensaouti, Y.; Stephanz, E.P.; Yu, T.-S.; Kernie, S.G. ApoE Regulates the Development of Adult Newborn Hippocampal Neurons. eNeuro 2018, 5, ENEURO.0155-18.2018. [Google Scholar] [CrossRef] [Green Version]
- Khalil, Y.A.; Rabès, J.-P.; Boileau, C.; Varret, M. APOE Gene Variants in Primary Dyslipidemia. Atherosclerosis 2021, 328, 11–22. [Google Scholar] [CrossRef]
- Verghese, P.B.; Castellano, J.M.; Holtzman, D.M. Apolipoprotein E in Alzheimer’s Disease and Other Neurological Disorders. Lancet Neurol. 2011, 10, 241–252. [Google Scholar] [CrossRef] [Green Version]
- Federoff, M.; Jimenez-Rolando, B.; Nalls, M.A.; Singleton, A.B. A Large Study Reveals No Association between APOE and Parkinson’s Disease. Neurobiol. Dis. 2012, 46, 389–392. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pu, J.; Jin, C.; Wang, Z.; Fang, Y.; Li, Y.; Xue, N.; Zheng, R.; Lin, Z.; Yan, Y.; Si, X.; et al. Apolipoprotein E Genotype Contributes to Motor Progression in Parkinson’s Disease. Mov. Disord. 2022, 37, 196–200. [Google Scholar] [CrossRef] [PubMed]
- Harrington, C.R.; Louwagie, J.; Rossau, R.; Vanmechelen, E.; Perry, R.H.; Perry, E.K.; Xuereb, J.H.; Roth, M.; Wischik, C.M. Influence of Apolipoprotein E Genotype on Senile Dementia of the Alzheimer and Lewy Body Types. Significance for Etiological Theories of Alzheimer’s Disease. Am. J. Pathol. 1994, 145, 1472–1484. [Google Scholar]
- Raman, S.; Brookhouser, N.; Brafman, D.A. Using Human Induced Pluripotent Stem Cells (HiPSCs) to Investigate the Mechanisms by Which Apolipoprotein E (APOE) Contributes to Alzheimer’s Disease (AD) Risk. Neurobiol. Dis. 2020, 138, 104788. [Google Scholar] [CrossRef]
- LaDu, M.J.; Falduto, M.T.; Manelli, A.M.; Reardon, C.A.; Getz, G.S.; Frail, D.E. Isoform-Specific Binding of Apolipoprotein E to Beta-Amyloid. J. Biol. Chem. 1994, 269, 23403–23406. [Google Scholar] [CrossRef]
- Lee, C.Y.D.; Landreth, G.E. The Role of Microglia in Amyloid Clearance from the AD Brain. J. Neural. Transm. 2010, 117, 949–960. [Google Scholar] [CrossRef] [Green Version]
- Deane, R.; Sagare, A.; Hamm, K.; Parisi, M.; Lane, S.; Finn, M.B.; Holtzman, D.M.; Zlokovic, B.V. ApoE Isoform-Specific Disruption of Amyloid Beta Peptide Clearance from Mouse Brain. J. Clin. Investig. 2008, 118, 4002–4013. [Google Scholar] [CrossRef] [Green Version]
- Verghese, P.B.; Castellano, J.M.; Garai, K.; Wang, Y.; Jiang, H.; Shah, A.; Bu, G.; Frieden, C.; Holtzman, D.M. ApoE Influences Amyloid-β (Aβ) Clearance despite Minimal ApoE/Aβ Association in Physiological Conditions. Proc. Natl. Acad. Sci. USA 2013, 110, E1807–E1816. [Google Scholar] [CrossRef] [Green Version]
- Jiang, Q.; Lee, C.Y.D.; Mandrekar, S.; Wilkinson, B.; Cramer, P.; Zelcer, N.; Mann, K.; Lamb, B.; Willson, T.M.; Collins, J.L.; et al. ApoE Promotes the Proteolytic Degradation of Abeta. Neuron 2008, 58, 681–693. [Google Scholar] [CrossRef] [Green Version]
- Wang, C.; Xiong, M.; Gratuze, M.; Bao, X.; Shi, Y.; Andhey, P.S.; Manis, M.; Schroeder, C.; Yin, Z.; Madore, C.; et al. Selective Removal of Astrocytic APOE4 Strongly Protects against Tau-Mediated Neurodegeneration and Decreases Synaptic Phagocytosis by Microglia. Neuron 2021, 109, 1657–1674.e7. [Google Scholar] [CrossRef] [PubMed]
- Hamanaka, H.; Katoh-Fukui, Y.; Suzuki, K.; Kobayashi, M.; Suzuki, R.; Motegi, Y.; Nakahara, Y.; Takeshita, A.; Kawai, M.; Ishiguro, K.; et al. Altered Cholesterol Metabolism in Human Apolipoprotein E4 Knock-in Mice. Hum. Mol. Genet. 2000, 9, 353–361. [Google Scholar] [CrossRef] [PubMed]
- Har-Paz, I.; Arieli, E.; Moran, A. ApoE4 Attenuates Cortical Neuronal Activity in Young Behaving ApoE4 Rats. Neurobiol. Dis. 2021, 155, 105373. [Google Scholar] [CrossRef] [PubMed]
- Har-Paz, I.; Roisman, N.; Michaelson, D.M.; Moran, A. Extra-Hippocampal Learning Deficits in Young Apolipoprotein E4 Mice and Their Synaptic Underpinning. JAD 2019, 72, 71–82. [Google Scholar] [CrossRef] [PubMed]
- Lanfranco, M.F.; Sepulveda, J.; Kopetsky, G.; Rebeck, G.W. Expression and Secretion of apoE Isoforms in Astrocytes and Microglia during Inflammation. Glia 2021, 69, 1478–1493. [Google Scholar] [CrossRef]
- Iannucci, J.; Sen, A.; Grammas, P. Isoform-Specific Effects of Apolipoprotein E on Markers of Inflammation and Toxicity in Brain Glia and Neuronal Cells In Vitro. CIMB 2021, 43, 215–225. [Google Scholar] [CrossRef]
- Nguyen, H.C.; Qadura, M.; Singh, K.K. Role of the Fatty Acid Binding Proteins in Cardiovascular Diseases: A Systematic Review. J. Clin. Med. 2020, 9, 3390. [Google Scholar] [CrossRef]
- Liu, R.-Z.; Mita, R.; Beaulieu, M.; Gao, Z.; Godbout, R. Fatty Acid Binding Proteins in Brain Development and Disease. Int. J. Dev. Biol. 2010, 54, 1229–1239. [Google Scholar] [CrossRef]
- Veerkamp, J.H.; Zimmerman, A.W. Fatty Acid-Binding Proteins of Nervous Tissue. JMN 2001, 16, 133–142. [Google Scholar] [CrossRef]
- Islam, A.; Kagawa, Y.; Sharifi, K.; Ebrahimi, M.; Miyazaki, H.; Yasumoto, Y.; Kawamura, S.; Yamamoto, Y.; Sakaguti, S.; Sawada, T.; et al. Fatty Acid Binding Protein 3 Is Involved in n–3 and n–6 PUFA Transport in Mouse Trophoblasts. J. Nutr. 2014, 144, 1509–1516. [Google Scholar] [CrossRef] [Green Version]
- Oizumi, H.; Yamasaki, K.; Suzuki, H.; Hasegawa, T.; Sugimura, Y.; Baba, T.; Fukunaga, K.; Takeda, A. Fatty Acid-Binding Protein 3 Expression in the Brain and Skin in Human Synucleinopathies. Front. Aging Neurosci. 2021, 13, 648982. [Google Scholar] [CrossRef] [PubMed]
- Shibasaki, Y.; Baillie, D.A.; St Clair, D.; Brookes, A.J. High-Resolution Mapping of SNCA Encoding Alpha-Synuclein, the Non-A Beta Component of Alzheimer’s Disease Amyloid Precursor, to Human Chromosome 4q21.3-->q22 by Fluorescence in Situ Hybridization. Cytogenet. Cell Genet. 1995, 71, 54–55. [Google Scholar] [CrossRef] [PubMed]
- Lashuel, H.A.; Overk, C.R.; Oueslati, A.; Masliah, E. The Many Faces of α-Synuclein: From Structure and Toxicity to Therapeutic Target. Nat. Rev. Neurosci. 2013, 14, 38–48. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Daniele, S.; Costa, B.; Pietrobono, D.; Giacomelli, C.; Iofrida, C.; Trincavelli, M.L.; Fusi, J.; Franzoni, F.; Martini, C. Epigenetic Modifications of the α-Synuclein Gene and Relative Protein Content Are Affected by Ageing and Physical Exercise in Blood from Healthy Subjects. Oxid Med. Cell. Longev. 2018, 2018, 3740345. [Google Scholar] [CrossRef] [Green Version]
- Villar-Piqué, A.; Lopes da Fonseca, T.; Outeiro, T.F. Structure, Function and Toxicity of Alpha-Synuclein: The Bermuda Triangle in Synucleinopathies. J. Neurochem. 2016, 139, 240–255. [Google Scholar] [CrossRef]
- Vargas, K.J.; Makani, S.; Davis, T.; Westphal, C.H.; Castillo, P.E.; Chandra, S.S. Synucleins Regulate the Kinetics of Synaptic Vesicle Endocytosis. J Neurosci. 2014, 34, 9364–9376. [Google Scholar] [CrossRef]
- Matsuo, K.; Kawahata, I.; Melki, R.; Bousset, L.; Owada, Y.; Fukunaga, K. Suppression of α-Synuclein Propagation after Intrastriatal Injection in FABP3 Null Mice. Brain Res. 2021, 1760, 147383. [Google Scholar] [CrossRef]
- Kawahata, I.; Fukunaga, K. Impact of Fatty Acid-Binding Proteins and Dopamine Receptors on α-Synucleinopathy. J. Pharmacol. Sci. 2022, 148, 248–254. [Google Scholar] [CrossRef]
- Pacheco, C.R.; Morales, C.N.; Ramírez, A.E.; Muñoz, F.J.; Gallegos, S.S.; Caviedes, P.A.; Aguayo, L.G.; Opazo, C.M. Extracellular α-Synuclein Alters Synaptic Transmission in Brain Neurons by Perforating the Neuronal Plasma Membrane. J. Neurochem. 2015, 132, 731–741. [Google Scholar] [CrossRef] [Green Version]
- Chen, L.; Jin, J.; Davis, J.; Zhou, Y.; Wang, Y.; Liu, J.; Lockhart, P.J.; Zhang, J. Oligomeric Alpha-Synuclein Inhibits Tubulin Polymerization. Biochem. Biophys. Res. Commun. 2007, 356, 548–553. [Google Scholar] [CrossRef]
- Kröger, H.; Donner, I.; Skiello, G. Influence of a New Virostatic Compound on the Induction of Enzymes in Rat Liver. Arzneimittelforschung 1975, 25, 1426–1429. [Google Scholar] [PubMed]
- Colla, E.; Coune, P.; Liu, Y.; Pletnikova, O.; Troncoso, J.C.; Iwatsubo, T.; Schneider, B.L.; Lee, M.K. Endoplasmic Reticulum Stress Is Important for the Manifestations of α-Synucleinopathy in Vivo. J. Neurosci. 2012, 32, 3306–3320. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klegeris, A.; Pelech, S.; Giasson, B.I.; Maguire, J.; Zhang, H.; McGeer, E.G.; McGeer, P.L. α-Synuclein Activates Stress Signaling Protein Kinases in THP-1 Cells and Microglia. Neurobiol. Aging 2008, 29, 739–752. [Google Scholar] [CrossRef] [PubMed]
- Wang, G.; Pan, J.; Chen, S.-D. Kinases and Kinase Signaling Pathways: Potential Therapeutic Targets in Parkinson’s Disease. Prog. Neurobiol. 2012, 98, 207–221. [Google Scholar] [CrossRef] [PubMed]
- Alvarez-Erviti, L.; Couch, Y.; Richardson, J.; Cooper, J.M.; Wood, M.J.A. Alpha-Synuclein Release by Neurons Activates the Inflammatory Response in a Microglial Cell Line. Neurosci. Res. 2011, 69, 337–342. [Google Scholar] [CrossRef]
- Brosseron, F.; Kleemann, K.; Kolbe, C.; Santarelli, F.; Castro-Gomez, S.; Tacik, P.; Latz, E.; Jessen, F.; Heneka, M.T. Interrelations of Alzheimer´s Disease Candidate Biomarkers Neurogranin, Fatty Acid-binding Protein 3 and Ferritin to Neurodegeneration and Neuroinflammation. J. Neurochem. 2021, 157, 2210–2224. [Google Scholar] [CrossRef]
- Dulewicz, M.; Kulczyńska-Przybik, A.; Słowik, A.; Borawska, R.; Mroczko, B. Fatty Acid Binding Protein 3 (FABP3) and Apolipoprotein E4 (ApoE4) as Lipid Metabolism-Related Biomarkers of Alzheimer’s Disease. JCM 2021, 10, 3009. [Google Scholar] [CrossRef]
- Sepe, F.N.; Chiasserini, D.; Parnetti, L. Role of FABP3 as Biomarker in Alzheimer’s Disease and Synucleinopathies. Future Neurol. 2018, 13, 199–207. [Google Scholar] [CrossRef] [Green Version]
- Marion, M.; Hamilton, J.; Richardson, B.; Roeder, N.; Figueiredo, A.; Nubelo, A.; Hetelekides, E.; Penman, S.; Owada, Y.; Kagawa, Y.; et al. Environmental Enrichment Sex-Dependently Rescues Memory Impairment in FABP5 KO Mice Not Mediated by Brain-Derived Neurotrophic Factor. Behav. Brain Res. 2022, 425, 113814. [Google Scholar] [CrossRef]
- Pan, Y.; Scanlon, M.J.; Owada, Y.; Yamamoto, Y.; Porter, C.J.H.; Nicolazzo, J.A. Fatty Acid-Binding Protein 5 Facilitates the Blood–Brain Barrier Transport of Docosahexaenoic Acid. Mol. Pharm. 2015, 12, 4375–4385. [Google Scholar] [CrossRef]
- Lauritzen, L.; Brambilla, P.; Mazzocchi, A.; Harsløf, L.; Ciappolino, V.; Agostoni, C. DHA Effects in Brain Development and Function. Nutrients 2016, 8, 6. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Shinoda, Y.; Cheng, A.; Kawahata, I.; Fukunaga, K. Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress. Biomedicines 2021, 9, 110. [Google Scholar] [CrossRef] [PubMed]
- Macdonald, R.; Barnes, K.; Hastings, C.; Mortiboys, H. Mitochondrial Abnormalities in Parkinson’s Disease and Alzheimer’s Disease: Can Mitochondria Be Targeted Therapeutically? Biochem. Soc. Trans. 2018, 46, 891–909. [Google Scholar] [CrossRef]
- Vicario, M.; Cieri, D.; Brini, M.; Calì, T. The Close Encounter Between Alpha-Synuclein and Mitochondria. Front. Neurosci. 2018, 12, 388. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Calì, T.; Ottolini, D.; Negro, A.; Brini, M. α-Synuclein Controls Mitochondrial Calcium Homeostasis by Enhancing Endoplasmic Reticulum-Mitochondria Interactions. J. Biol. Chem. 2012, 287, 17914–17929. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pozo Devoto, V.M.; Dimopoulos, N.; Alloatti, M.; Pardi, M.B.; Saez, T.M.; Otero, M.G.; Cromberg, L.E.; Marín-Burgin, A.; Scassa, M.E.; Stokin, G.B.; et al. αSynuclein Control of Mitochondrial Homeostasis in Human-Derived Neurons Is Disrupted by Mutations Associated with Parkinson’s Disease. Sci. Rep. 2017, 7, 5042. [Google Scholar] [CrossRef] [Green Version]
- Menges, S.; Minakaki, G.; Schaefer, P.M.; Meixner, H.; Prots, I.; Schlötzer-Schrehardt, U.; Friedland, K.; Winner, B.; Outeiro, T.F.; Winklhofer, K.F.; et al. Alpha-Synuclein Prevents the Formation of Spherical Mitochondria and Apoptosis under Oxidative Stress. Sci. Rep. 2017, 7, 42942. [Google Scholar] [CrossRef] [Green Version]
- Gui, Y.-X.; Wang, X.-Y.; Kang, W.-Y.; Zhang, Y.-J.; Zhang, Y.; Zhou, Y.; Quinn, T.J.; Liu, J.; Chen, S.-D. Extracellular Signal-Regulated Kinase Is Involved in Alpha-Synuclein-Induced Mitochondrial Dynamic Disorders by Regulating Dynamin-like Protein 1. Neurobiol. Aging 2012, 33, 2841–2854. [Google Scholar] [CrossRef]
- Devi, L.; Raghavendran, V.; Prabhu, B.M.; Avadhani, N.G.; Anandatheerthavarada, H.K. Mitochondrial Import and Accumulation of α-Synuclein Impair Complex I in Human Dopaminergic Neuronal Cultures and Parkinson Disease Brain. J. Biol. Chem. 2008, 283, 9089–9100. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.; Wahafu, A.; Wu, W.; Xiang, J.; Huo, L.; Ma, X.; Wang, N.; Liu, H.; Bai, X.; Xu, D.; et al. FABP5 Enhances Malignancies of Lower-grade Gliomas via Canonical Activation of NF-κB Signaling. J. Cell. Mol. Med. 2021, 25, 4487–4500. [Google Scholar] [CrossRef]
- Kipp, M.; Clarner, T.; Gingele, S.; Pott, F.; Amor, S.; van der Valk, P.; Beyer, C. Brain Lipid Binding Protein (FABP7) as Modulator of Astrocyte Function. Physiol. Res. 2011, 60, S49–S60. [Google Scholar] [CrossRef] [PubMed]
- Ebrahimi, M.; Yamamoto, Y.; Sharifi, K.; Kida, H.; Kagawa, Y.; Yasumoto, Y.; Islam, A.; Miyazaki, H.; Shimamoto, C.; Maekawa, M.; et al. Astrocyte-Expressed FABP7 Regulates Dendritic Morphology and Excitatory Synaptic Function of Cortical Neurons: Astrocyte FABP7 as a Regulator of Neuronal Morphology. Glia 2016, 64, 48–62. [Google Scholar] [CrossRef] [PubMed]
- Killoy, K.M.; Harlan, B.A.; Pehar, M.; Vargas, M.R. FABP7 Upregulation Induces a Neurotoxic Phenotype in Astrocytes. Glia 2020, 68, 2693–2704. [Google Scholar] [CrossRef] [PubMed]
- Elsherbiny, M.E.; Emara, M.; Godbout, R. Interaction of Brain Fatty Acid-Binding Protein with the Polyunsaturated Fatty Acid Environment as a Potential Determinant of Poor Prognosis in Malignant Glioma. Prog. Lipid Res. 2013, 52, 562–570. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Asaro, A.; Sinha, R.; Bakun, M.; Kalnytska, O.; Carlo-Spiewok, A.-S.; Rubel, T.; Rozeboom, A.; Dadlez, M.; Kaminska, B.; Aronica, E.; et al. ApoE4 Disrupts Interaction of Sortilin with Fatty Acid-Binding Protein 7 Essential to Promote Lipid Signaling. J. Cell. Sci. 2021, 134, jcs258894. [Google Scholar] [CrossRef]
- Duffy, C.M.; Xu, H.; Nixon, J.P.; Bernlohr, D.A.; Butterick, T.A. Identification of a Fatty Acid Binding Protein4-UCP2 Axis Regulating Microglial Mediated Neuroinflammation. Mol. Cell. Neurosci. 2017, 80, 52–57. [Google Scholar] [CrossRef] [Green Version]
- McFarlane, O.; Kędziora-Kornatowska, K. Cholesterol and Dementia: A Long and Complicated Relationship. CAS 2020, 13, 42–51. [Google Scholar] [CrossRef]
- Noguchi, N.; Saito, Y.; Urano, Y. Diverse Functions of 24(S)-Hydroxycholesterol in the Brain. Biochem. Biophys. Res. Commun. 2014, 446, 692–696. [Google Scholar] [CrossRef]
- Goedeke, L.; Fernández-Hernando, C. MicroRNAs: A Connection between Cholesterol Metabolism and Neurodegeneration. Neurobiol. Dis. 2014, 72, 48–53. [Google Scholar] [CrossRef] [Green Version]
- Gamba, P.; Testa, G.; Gargiulo, S.; Staurenghi, E.; Poli, G.; Leonarduzzi, G. Oxidized Cholesterol as the Driving Force behind the Development of Alzheimer’s Disease. Front. Aging Neurosci. 2015, 7, 119. [Google Scholar] [CrossRef] [Green Version]
- George, K.S.; Wu, S. Lipid Raft: A Floating Island of Death or Survival. Toxicol. Appl. Pharmacol. 2012, 259, 311–319. [Google Scholar] [CrossRef]
- García-Sanz, P.; Aerts, J.; Moratalla, R. The Role of Cholesterol in α-Synuclein and Lewy Body Pathology in GBA1 Parkinson’s Disease. Mov. Disord. 2021, 36, 1070–1085. [Google Scholar] [CrossRef] [PubMed]
- García-Sanz, P.; Orgaz, L.; Bueno-Gil, G.; Espadas, I.; Rodríguez-Traver, E.; Kulisevsky, J.; Gutierrez, A.; Dávila, J.C.; González-Polo, R.A.; Fuentes, J.M.; et al. N370S -GBA1 Mutation Causes Lysosomal Cholesterol Accumulation in Parkinson’s Disease: Cholesterol Accumulates in GBA1 -PD Lysosomes. Mov. Disord. 2017, 32, 1409–1422. [Google Scholar] [CrossRef] [PubMed]
- García-Sanz, P.; Orgaz, L.; Fuentes, J.M.; Vicario, C.; Moratalla, R. Cholesterol and Multilamellar Bodies: Lysosomal Dysfunction in GBA -Parkinson Disease. Autophagy 2018, 14, 717–718. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Snezhkina, A.V.; Kudryavtseva, A.V.; Kardymon, O.L.; Savvateeva, M.V.; Melnikova, N.V.; Krasnov, G.S.; Dmitriev, A.A. ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells. Oxid. Med. Cell. Longev. 2019, 2019, 6175804. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schieber, M.; Chandel, N.S. ROS Function in Redox Signaling and Oxidative Stress. Curr. Biol. 2014, 24, R453–R462. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oktyabrsky, O.N.; Smirnova, G.V. Redox Regulation of Cellular Functions. Biochemistry 2007, 72, 132–145. [Google Scholar] [CrossRef] [PubMed]
- Lennicke, C.; Cochemé, H.M. Redox Metabolism: ROS as Specific Molecular Regulators of Cell Signaling and Function. Mol. Cell 2021, 81, 3691–3707. [Google Scholar] [CrossRef]
- Sultana, R.; Perluigi, M.; Butterfield, D.A. Lipid Peroxidation Triggers Neurodegeneration: A Redox Proteomics View into the Alzheimer Disease Brain. Free Radic. Biol. Med. 2013, 62, 157–169. [Google Scholar] [CrossRef] [Green Version]
- Angelova, P.R.; Esteras, N.; Abramov, A.Y. Mitochondria and Lipid Peroxidation in the Mechanism of Neurodegeneration: Finding Ways for Prevention. Med. Res. Rev. 2021, 41, 770–784. [Google Scholar] [CrossRef]
- Angelova, P.R.; Abramov, A.Y. Functional Role of Mitochondrial Reactive Oxygen Species in Physiology. Free Radic. Biol. Med. 2016, 100, 81–85. [Google Scholar] [CrossRef] [PubMed]
- Abramov, A.Y.; Scorziello, A.; Duchen, M.R. Three Distinct Mechanisms Generate Oxygen Free Radicals in Neurons and Contribute to Cell Death during Anoxia and Reoxygenation. J. Neurosci. 2007, 27, 1129–1138. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gandhi, S.; Abramov, A.Y. Mechanism of Oxidative Stress in Neurodegeneration. Oxid. Med. Cell. Longev. 2012, 2012, 428010. [Google Scholar] [CrossRef] [Green Version]
- Shichiri, M. The Role of Lipid Peroxidation in Neurological Disorders. J. Clin. Biochem. Nutr. 2014, 54, 151–160. [Google Scholar] [CrossRef] [Green Version]
- Petrovic, S.; Arsic, A.; Ristic-Medic, D.; Cvetkovic, Z.; Vucic, V. Lipid Peroxidation and Antioxidant Supplementation in Neurodegenerative Diseases: A Review of Human Studies. Antioxidants 2020, 9, 1128. [Google Scholar] [CrossRef]
- Tadokoro, K.; Ohta, Y.; Inufusa, H.; Loon, A.F.N.; Abe, K. Prevention of Cognitive Decline in Alzheimer’s Disease by Novel Antioxidative Supplements. IJMS 2020, 21, 1974. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Butterfield, D.A.; Mattson, M.P. Apolipoprotein E and Oxidative Stress in Brain with Relevance to Alzheimer’s Disease. Neurobiol. Dis. 2020, 138, 104795. [Google Scholar] [CrossRef] [PubMed]
- Farooqui, A.A.; Horrocks, L.A. Lipid Peroxides in the Free Radical Pathophysiology of Brain Diseases. Cell. Mol. Neurobiol. 1998, 18, 599–608. [Google Scholar] [CrossRef]
- Anzai, K.; Ogawa, K.; Goto, Y.; Senzaki, Y.; Ozawa, T.; Yamamoto, H. Oxidation-Dependent Changes in the Stability and Permeability of Lipid Bilayers. Antioxid Redox Signal. 1999, 1, 339–347. [Google Scholar] [CrossRef]
- Yehuda, S.; Rabinovitz, S.; Carasso, R.L.; Mostofsky, D.I. The Role of Polyunsaturated Fatty Acids in Restoring the Aging Neuronal Membrane. Neurobiol. Aging 2002, 23, 843–853. [Google Scholar] [CrossRef] [Green Version]
- Moreira, P.I.; Santos, M.S.; Oliveira, C.R.; Shenk, J.C.; Nunomura, A.; Smith, M.A.; Zhu, X.; Perry, G. Alzheimer Disease and the Role of Free Radicals in the Pathogenesis of the Disease. CNS Neurol. Disord. Drug Targets 2008, 7, 3–10. [Google Scholar] [CrossRef] [PubMed]
- Daniele, S.; Giacomelli, C.; Martini, C. Brain Ageing and Neurodegenerative Disease: The Role of Cellular Waste Management. Biochem. Pharmacol. 2018, 158, 207–216. [Google Scholar] [CrossRef] [PubMed]
- Giacomelli, C.; Daniele, S.; Martini, C. Potential Biomarkers and Novel Pharmacological Targets in Protein Aggregation-Related Neurodegenerative Diseases. Biochem. Pharmacol. 2017, 131, 1–15. [Google Scholar] [CrossRef]
- Butterfield, D.A.; Bader Lange, M.L.; Sultana, R. Involvements of the Lipid Peroxidation Product, HNE, in the Pathogenesis and Progression of Alzheimer’s Disease. Biochim. Biophys. Acta 2010, 1801, 924–929. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, J.; Kosaras, B.; Del Signore, S.J.; Cormier, K.; McKee, A.; Ratan, R.R.; Kowall, N.W.; Ryu, H. Modulation of Lipid Peroxidation and Mitochondrial Function Improves Neuropathology in Huntington’s Disease Mice. Acta Neuropathol. 2011, 121, 487–498. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ruipérez, V.; Darios, F.; Davletov, B. Alpha-Synuclein, Lipids and Parkinson’s Disease. Prog. Lipid Res. 2010, 49, 420–428. [Google Scholar] [CrossRef]
- Sajdel-Sulkowska, E.M.; Marotta, C.A. Alzheimer’s Disease Brain: Alterations in RNA Levels and in a Ribonuclease-Inhibitor Complex. Science 1984, 225, 947–949. [Google Scholar] [CrossRef]
- Shichiri, M.; Yoshida, Y.; Ishida, N.; Hagihara, Y.; Iwahashi, H.; Tamai, H.; Niki, E. α-Tocopherol Suppresses Lipid Peroxidation and Behavioral and Cognitive Impairments in the Ts65Dn Mouse Model of Down Syndrome. Free Radic. Biol. Med. 2011, 50, 1801–1811. [Google Scholar] [CrossRef]
- Vaarmann, A.; Gandhi, S.; Abramov, A.Y. Dopamine Induces Ca2+ Signaling in Astrocytes through Reactive Oxygen Species Generated by Monoamine Oxidase. J. Biol. Chem. 2010, 285, 25018–25023. [Google Scholar] [CrossRef] [Green Version]
- Ademowo, O.S.; Dias, H.K.I.; Burton, D.G.A.; Griffiths, H.R. Lipid (per) Oxidation in Mitochondria: An Emerging Target in the Ageing Process? Biogerontology 2017, 18, 859–879. [Google Scholar] [CrossRef] [Green Version]
- Shen, Z.; Ye, C.; McCain, K.; Greenberg, M.L. The Role of Cardiolipin in Cardiovascular Health. Biomed Res. Int. 2015, 2015, 891707. [Google Scholar] [CrossRef] [PubMed]
- Pienaar, I.S.; Elson, J.L.; Racca, C.; Nelson, G.; Turnbull, D.M.; Morris, C.M. Mitochondrial Abnormality Associates with Type-Specific Neuronal Loss and Cell Morphology Changes in the Pedunculopontine Nucleus in Parkinson Disease. Am. J. Pathol. 2013, 183, 1826–1840. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chandrasekaran, K.; Giordano, T.; Brady, D.R.; Stoll, J.; Martin, L.J.; Rapoport, S.I. Impairment in Mitochondrial Cytochrome Oxidase Gene Expression in Alzheimer Disease. Mol. Brain Res. 1994, 24, 336–340. [Google Scholar] [CrossRef]
- Chen, L.; Na, R.; Gu, M.; Richardson, A.; Ran, Q. Lipid Peroxidation Up-Regulates BACE1 Expression in Vivo: A Possible Early Event of Amyloidogenesis in Alzheimer’s Disease. J. Neurochem. 2008, 107, 197–207. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tan, B.L.; Norhaizan, M.E.; Liew, W.-P.-P.; Sulaiman Rahman, H. Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases. Front. Pharmacol. 2018, 9, 1162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oppedisano, F.; Maiuolo, J.; Gliozzi, M.; Musolino, V.; Carresi, C.; Nucera, S.; Scicchitano, M.; Scarano, F.; Bosco, F.; Macrì, R.; et al. The Potential for Natural Antioxidant Supplementation in the Early Stages of Neurodegenerative Disorders. IJMS 2020, 21, 2618. [Google Scholar] [CrossRef] [Green Version]
- Kontush, A.; Mann, U.; Arlt, S.; Ujeyl, A.; Lührs, C.; Müller-Thomsen, T.; Beisiegel, U. Influence of Vitamin E and C Supplementation on Lipoprotein Oxidation in Patients with Alzheimer’s Disease. Free Radic. Biol. Med. 2001, 31, 345–354. [Google Scholar] [CrossRef]
- Kiecolt-Glaser, J.K.; Epel, E.S.; Belury, M.A.; Andridge, R.; Lin, J.; Glaser, R.; Malarkey, W.B.; Hwang, B.S.; Blackburn, E. Omega-3 Fatty Acids, Oxidative Stress, and Leukocyte Telomere Length: A Randomized Controlled Trial. Brain Behav. Immun. 2013, 28, 16–24. [Google Scholar] [CrossRef] [Green Version]
- Mohammad, N.S.; Nazli, R.; Zafar, H.; Fatima, S. Effects of Lipid Based Multiple Micronutrients Supplement on the Birth Outcome of Underweight Pre-Eclamptic Women: A Randomized Clinical Trial. Pak. J. Med. Sci. 2022, 38, 219–226. [Google Scholar] [CrossRef]
- Moss, J.W.E.; Williams, J.O.; Ramji, D.P. Nutraceuticals as Therapeutic Agents for Atherosclerosis. Biochim. Biophys. Acta Mol. Basis Dis. 2018, 1864, 1562–1572. [Google Scholar] [CrossRef]
- Ribeiro, S.M.L.; Luz, S.D.S.; Aquino, R.d.C. The Role of Nutrition and Physical Activity in Cholesterol and Aging. Clin. Geriatr. Med. 2015, 31, 401–416. [Google Scholar] [CrossRef] [PubMed]
- Demonty, I.; Ras, R.T.; van der Knaap, H.C.M.; Duchateau, G.S.M.J.E.; Meijer, L.; Zock, P.L.; Geleijnse, J.M.; Trautwein, E.A. Continuous Dose-Response Relationship of the LDL-Cholesterol-Lowering Effect of Phytosterol Intake. J. Nutr. 2009, 139, 271–284. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kaur, R.; Myrie, S.B. Association of Dietary Phytosterols with Cardiovascular Disease Biomarkers in Humans. Lipids 2020, 55, 569–584. [Google Scholar] [CrossRef] [PubMed]
- Mooradian, A.D.; Haas, M.J. The Effect of Nutritional Supplements on Serum High-Density Lipoprotein Cholesterol and Apolipoprotein A-I. Am. J. Cardiovasc. Drugs 2014, 14, 253–274. [Google Scholar] [CrossRef] [PubMed]
- Xu, Y.; Nisenblat, V.; Lu, C.; Li, R.; Qiao, J.; Zhen, X.; Wang, S. Pretreatment with Coenzyme Q10 Improves Ovarian Response and Embryo Quality in Low-Prognosis Young Women with Decreased Ovarian Reserve: A Randomized Controlled Trial. Reprod Biol. Endocrinol. 2018, 16, 29. [Google Scholar] [CrossRef] [Green Version]
- Sawaddiruk, P.; Apaijai, N.; Paiboonworachat, S.; Kaewchur, T.; Kasitanon, N.; Jaiwongkam, T.; Kerdphoo, S.; Chattipakorn, N.; Chattipakorn, S.C. Coenzyme Q10 Supplementation Alleviates Pain in Pregabalin-Treated Fibromyalgia Patients via Reducing Brain Activity and Mitochondrial Dysfunction. Free Radic. Res. 2019, 53, 901–909. [Google Scholar] [CrossRef]
- Mischley, L.K.; Allen, J.; Bradley, R. Coenzyme Q10 Deficiency in Patients with Parkinson’s Disease. J. Neurol. Sci. 2012, 318, 72–75. [Google Scholar] [CrossRef] [Green Version]
- Moussa, C.; Hebron, M.; Huang, X.; Ahn, J.; Rissman, R.A.; Aisen, P.S.; Turner, R.S. Resveratrol Regulates Neuro-Inflammation and Induces Adaptive Immunity in Alzheimer’s Disease. J. Neuroinflam. 2017, 14, 1. [Google Scholar] [CrossRef] [Green Version]
- Bo, S.; Togliatto, G.; Gambino, R.; Ponzo, V.; Lombardo, G.; Rosato, R.; Cassader, M.; Brizzi, M.F. Impact of Sirtuin-1 Expression on H3K56 Acetylation and Oxidative Stress: A Double-Blind Randomized Controlled Trial with Resveratrol Supplementation. Acta Diabetol. 2018, 55, 331–340. [Google Scholar] [CrossRef] [Green Version]
- Ochiai, R.; Saitou, K.; Suzukamo, C.; Osaki, N.; Asada, T. Effect of Chlorogenic Acids on Cognitive Function in Mild Cognitive Impairment: A Randomized Controlled Crossover Trial. JAD 2019, 72, 1209–1216. [Google Scholar] [CrossRef] [Green Version]
- Oboh, G.; Agunloye, O.M.; Akinyemi, A.J.; Ademiluyi, A.O.; Adefegha, S.A. Comparative Study on the Inhibitory Effect of Caffeic and Chlorogenic Acids on Key Enzymes Linked to Alzheimer’s Disease and Some Pro-Oxidant Induced Oxidative Stress in Rats’ Brain-In Vitro. Neurochem. Res. 2013, 38, 413–419. [Google Scholar] [CrossRef] [PubMed]
- Samarghandian, S.; Azimi-Nezhad, M.; Farkhondeh, T.; Samini, F. Anti-Oxidative Effects of Curcumin on Immobilization-Induced Oxidative Stress in Rat Brain, Liver and Kidney. Biomed. Pharmacother. 2017, 87, 223–229. [Google Scholar] [CrossRef] [PubMed]
- Taïlé, J.; Arcambal, A.; Clerc, P.; Gauvin-Bialecki, A.; Gonthier, M.-P. Medicinal Plant Polyphenols Attenuate Oxidative Stress and Improve Inflammatory and Vasoactive Markers in Cerebral Endothelial Cells during Hyperglycemic Condition. Antioxidants 2020, 9, 573. [Google Scholar] [CrossRef] [PubMed]
- Cicero, A.F.G.; Colletti, A. Polyphenols Effect on Circulating Lipids and Lipoproteins: From Biochemistry to Clinical Evidence. Curr. Pharm. Des. 2018, 24, 178–190. [Google Scholar] [CrossRef]
- Castro-Barquero, S.; Tresserra-Rimbau, A.; Vitelli-Storelli, F.; Doménech, M.; Salas-Salvadó, J.; Martín-Sánchez, V.; Rubín-García, M.; Buil-Cosiales, P.; Corella, D.; Fitó, M.; et al. Dietary Polyphenol Intake Is Associated with HDL-Cholesterol and A Better Profile of Other Components of the Metabolic Syndrome: A PREDIMED-Plus Sub-Study. Nutrients 2020, 12, 689. [Google Scholar] [CrossRef] [Green Version]
- Kapiotis, S.; Hermann, M.; Held, I.; Seelos, C.; Ehringer, H.; Gmeiner, B.M. Genistein, the Dietary-Derived Angiogenesis Inhibitor, Prevents LDL Oxidation and Protects Endothelial Cells from Damage by Atherogenic LDL. Arter. Thromb. Vasc. Biol. 1997, 17, 2868–2874. [Google Scholar] [CrossRef]
- Demir, E.; Taysi, S.; Ulusal, H.; Kaplan, D.S.; Cinar, K.; Tarakcioglu, M. Nigella Sativa Oil and Thymoquinone Reduce Oxidative Stress in the Brain Tissue of Rats Exposed to Total Head Irradiation. Int. J. Radiat. Biol. 2020, 96, 228–235. [Google Scholar] [CrossRef]
- Jafari, F.; Amani, R.; Tarrahi, M.J. Effect of Zinc Supplementation on Physical and Psychological Symptoms, Biomarkers of Inflammation, Oxidative Stress, and Brain-Derived Neurotrophic Factor in Young Women with Premenstrual Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Biol. Trace Elem. Res. 2020, 194, 89–95. [Google Scholar] [CrossRef]
- Ebokaiwe, A.P.; Okori, S.; Nwankwo, J.O.; Ejike, C.E.C.C.; Osawe, S.O. Selenium Nanoparticles and Metformin Ameliorate Streptozotocin-Instigated Brain Oxidative-Inflammatory Stress and Neurobehavioral Alterations in Rats. Naunyn-Schmiedeberg’s Arch. Pharmacol. 2021, 394, 591–602. [Google Scholar] [CrossRef]
- Wu, J.Y.; Reaves, S.K.; Wang, Y.R.; Wu, Y.; Lei, P.P.; Lei, K.Y. Zinc Deficiency Decreases Plasma Level and Hepatic MRNA Abundance of Apolipoprotein A-I in Rats and Hamsters. Am. J. Physiol. 1998, 275, C1516–C1525. [Google Scholar] [CrossRef] [Green Version]
- Cheng, L.-H.; Liu, Y.-W.; Wu, C.-C.; Wang, S.; Tsai, Y.-C. Psychobiotics in Mental Health, Neurodegenerative and Neurodevelopmental Disorders. J. Food Drug Anal. 2019, 27, 632–648. [Google Scholar] [CrossRef] [PubMed]
- Athari Nik Azm, S.; Djazayeri, A.; Safa, M.; Azami, K.; Ahmadvand, B.; Sabbaghziarani, F.; Sharifzadeh, M.; Vafa, M. Lactobacilli and Bifidobacteria Ameliorate Memory and Learning Deficits and Oxidative Stress in β-Amyloid (1–42) Injected Rats. Appl. Physiol. Nutr. Metab. 2018, 43, 718–726. [Google Scholar] [CrossRef] [PubMed]
- Musa, N.H.; Mani, V.; Lim, S.M.; Vidyadaran, S.; Abdul Majeed, A.B.; Ramasamy, K. Lactobacilli-Fermented Cow’s Milk Attenuated Lipopolysaccharide-Induced Neuroinflammation and Memory Impairment in Vitro and in Vivo. J. Dairy Res. 2017, 84, 488–495. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Akbari, E.; Asemi, Z.; Daneshvar Kakhaki, R.; Bahmani, F.; Kouchaki, E.; Tamtaji, O.R.; Hamidi, G.A.; Salami, M. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer’s Disease: A Randomized, Double-Blind and Controlled Trial. Front. Aging Neurosci. 2016, 8, 256. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bonfili, L.; Cecarini, V.; Cuccioloni, M.; Angeletti, M.; Berardi, S.; Scarpona, S.; Rossi, G.; Eleuteri, A.M. SLAB51 Probiotic Formulation Activates SIRT1 Pathway Promoting Antioxidant and Neuroprotective Effects in an AD Mouse Model. Mol. Neurobiol. 2018, 55, 7987–8000. [Google Scholar] [CrossRef] [Green Version]
- Kim, D.; Nguyen, M.D.; Dobbin, M.M.; Fischer, A.; Sananbenesi, F.; Rodgers, J.T.; Delalle, I.; Baur, J.A.; Sui, G.; Armour, S.M.; et al. SIRT1 Deacetylase Protects against Neurodegeneration in Models for Alzheimer’s Disease and Amyotrophic Lateral Sclerosis. EMBO J. 2007, 26, 3169–3179. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tamtaji, O.R.; Taghizadeh, M.; Daneshvar Kakhaki, R.; Kouchaki, E.; Bahmani, F.; Borzabadi, S.; Oryan, S.; Mafi, A.; Asemi, Z. Clinical and Metabolic Response to Probiotic Administration in People with Parkinson’s Disease: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin. Nutr. 2019, 38, 1031–1035. [Google Scholar] [CrossRef]
- Borzabadi, S.; Oryan, S.; Eidi, A.; Aghadavod, E.; Daneshvar Kakhaki, R.; Tamtaji, O.R.; Taghizadeh, M.; Asemi, Z. The Effects of Probiotic Supplementation on Gene Expression Related to Inflammation, Insulin and Lipid in Patients with Parkinson’s Disease: A Randomized, Double-Blind, PlaceboControlled Trial. Arch. Iran. Med. 2018, 21, 289–295. [Google Scholar]
- Liu, Y.; Yan, T.; Chu, J.M.-T.; Chen, Y.; Dunnett, S.; Ho, Y.-S.; Wong, G.T.-C.; Chang, R.C.-C. The Beneficial Effects of Physical Exercise in the Brain and Related Pathophysiological Mechanisms in Neurodegenerative Diseases. Lab. Investig. 2019, 99, 943–957. [Google Scholar] [CrossRef]
- Erickson, K.I.; Voss, M.W.; Prakash, R.S.; Basak, C.; Szabo, A.; Chaddock, L.; Kim, J.S.; Heo, S.; Alves, H.; White, S.M.; et al. Exercise Training Increases Size of Hippocampus and Improves Memory. Proc. Natl. Acad. Sci. USA 2011, 108, 3017–3022. [Google Scholar] [CrossRef] [Green Version]
- Won, J.; Callow, D.D.; Pena, G.S.; Jordan, L.S.; Arnold-Nedimala, N.A.; Nielson, K.A.; Smith, J.C. Hippocampal Functional Connectivity and Memory Performance After Exercise Intervention in Older Adults with Mild Cognitive Impairment. JAD 2021, 82, 1015–1031. [Google Scholar] [CrossRef] [PubMed]
- Arazi, H.; Babaei, P.; Moghimi, M.; Asadi, A. Acute Effects of Strength and Endurance Exercise on Serum BDNF and IGF-1 Levels in Older Men. BMC Geriatr. 2021, 21, 50. [Google Scholar] [CrossRef] [PubMed]
- Colucci-D’Amato, L.; Speranza, L.; Volpicelli, F. Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. IJMS 2020, 21, 7777. [Google Scholar] [CrossRef] [PubMed]
- von Bohlen und Halbach, O.; von Bohlen und Halbach, V. BDNF Effects on Dendritic Spine Morphology and Hippocampal Function. Cell Tissue Res. 2018, 373, 729–741. [Google Scholar] [CrossRef]
- Lin, J.-Y.; Kuo, W.-W.; Baskaran, R.; Kuo, C.-H.; Chen, Y.-A.; Chen, W.S.-T.; Ho, T.-J.; Day, C.H.; Mahalakshmi, B.; Huang, C.-Y. Swimming Exercise Stimulates IGF1/ PI3K/Akt and AMPK/SIRT1/PGC1α Survival Signaling to Suppress Apoptosis and Inflammation in Aging Hippocampus. Aging 2020, 12, 6852–6864. [Google Scholar] [CrossRef]
- Scisciola, L.; Fontanella, R.A.; Surina; Cataldo, V.; Paolisso, G.; Barbieri, M. Sarcopenia and Cognitive Function: Role of Myokines in Muscle Brain Cross-Talk. Life 2021, 11, 173. [Google Scholar] [CrossRef]
- Wrann, C.D.; White, J.P.; Salogiannnis, J.; Laznik-Bogoslavski, D.; Wu, J.; Ma, D.; Lin, J.D.; Greenberg, M.E.; Spiegelman, B.M. Exercise Induces Hippocampal BDNF through a PGC-1α/FNDC5 Pathway. Cell Metab. 2013, 18, 649–659. [Google Scholar] [CrossRef] [Green Version]
- Lourenco, M.V.; Frozza, R.L.; de Freitas, G.B.; Zhang, H.; Kincheski, G.C.; Ribeiro, F.C.; Gonçalves, R.A.; Clarke, J.R.; Beckman, D.; Staniszewski, A.; et al. Exercise-Linked FNDC5/Irisin Rescues Synaptic Plasticity and Memory Defects in Alzheimer’s Models. Nat. Med. 2019, 25, 165–175. [Google Scholar] [CrossRef]
- Peng, J.; Deng, X.; Huang, W.; Yu, J.; Wang, J.; Wang, J.; Yang, S.; Liu, X.; Wang, L.; Zhang, Y.; et al. Irisin Protects against Neuronal Injury Induced by Oxygen-Glucose Deprivation in Part Depends on the Inhibition of ROS-NLRP3 Inflammatory Signaling Pathway. Mol. Immunol. 2017, 91, 185–194. [Google Scholar] [CrossRef]
- Abd El-Kader, S.M.; Al-Jiffri, O.H. Aerobic Exercise Modulates Cytokine Profile and Sleep Quality in Elderly. Afr. Health Sci. 2019, 19, 2198. [Google Scholar] [CrossRef] [Green Version]
- Abd El-Kader, S.M.; Al-Shreef, F.M. Inflammatory Cytokines and Immune System Modulation by Aerobic versus Resisted Exercise Training for Elderly. Afr. Health Sci. 2018, 18, 120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abd El-Kader, S.M.; Al-Shreef, F.M.; Al-Jiffri, O.H. Impact of Aerobic Exercise versus Resisted Exercise on Endothelial Activation Markers and Inflammatory Cytokines among Elderly. Afr. Health Sci. 1970, 19, 2874–2880. [Google Scholar] [CrossRef] [PubMed]
- Mee-Inta, O.; Zhao, Z.-W.; Kuo, Y.-M. Physical Exercise Inhibits Inflammation and Microglial Activation. Cells 2019, 8, 691. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Retracted: Treadmill Training Increases SIRT-1 and PGC-1 α Protein Levels and AMPK Phosphorylation in Quadriceps of Middle-Aged Rats in an Intensity-Dependent Manner. Mediat. Inflamm. 2017, 2017, 8287646. [CrossRef] [Green Version]
- Lu, Y.; Dong, Y.; Tucker, D.; Wang, R.; Ahmed, M.E.; Brann, D.; Zhang, Q. Treadmill Exercise Exerts Neuroprotection and Regulates Microglial Polarization and Oxidative Stress in a Streptozotocin-Induced Rat Model of Sporadic Alzheimer’s Disease. JAD 2017, 56, 1469–1484. [Google Scholar] [CrossRef] [Green Version]
- Boccatonda, A.; Tripaldi, R.; Davì, G.; Santilli, F. Oxidative Stress Modulation Through Habitual Physical Activity. CPD 2016, 22, 3648–3680. [Google Scholar] [CrossRef]
- Pingitore, A.; Lima, G.P.P.; Mastorci, F.; Quinones, A.; Iervasi, G.; Vassalle, C. Exercise and Oxidative Stress: Potential Effects of Antioxidant Dietary Strategies in Sports. Nutrition 2015, 31, 916–922. [Google Scholar] [CrossRef]
- Cammisuli, D.M.; Bonuccelli, U.; Daniele, S.; Martini, C.; Fusi, J.; Franzoni, F. Aerobic Exercise and Healthy Nutrition as Neuroprotective Agents for Brain Health in Patients with Parkinson’s Disease: A Critical Review of the Literature. Antioxidants 2020, 9, 380. [Google Scholar] [CrossRef]
- Piccarducci, R.; Daniele, S.; Fusi, J.; Chico, L.; Baldacci, F.; Siciliano, G.; Bonuccelli, U.; Franzoni, F.; Martini, C. Impact of ApoE Polymorphism and Physical Activity on Plasma Antioxidant Capability and Erythrocyte Membranes. Antioxidants 2019, 8, 538. [Google Scholar] [CrossRef] [Green Version]
- Nawaz, A.; Batool, Z.; Shazad, S.; Rafiq, S.; Afzal, A.; Haider, S. Physical Enrichment Enhances Memory Function by Regulating Stress Hormone and Brain Acetylcholinesterase Activity in Rats Exposed to Restraint Stress. Life Sci. 2018, 207, 42–49. [Google Scholar] [CrossRef]
- Haider, S.; Saleem, S.; Perveen, T.; Tabassum, S.; Batool, Z.; Sadir, S.; Liaquat, L.; Madiha, S. Age-Related Learning and Memory Deficits in Rats: Role of Altered Brain Neurotransmitters, Acetylcholinesterase Activity and Changes in Antioxidant Defense System. AGE 2014, 36, 9653. [Google Scholar] [CrossRef] [PubMed]
- Pekny, M.; Wilhelmsson, U.; Pekna, M. The Dual Role of Astrocyte Activation and Reactive Gliosis. Neurosci. Lett. 2014, 565, 30–38. [Google Scholar] [CrossRef] [PubMed]
- Belaya, I.; Ivanova, M.; Sorvari, A.; Ilicic, M.; Loppi, S.; Koivisto, H.; Varricchio, A.; Tikkanen, H.; Walker, F.R.; Atalay, M.; et al. Astrocyte Remodeling in the Beneficial Effects of Long-Term Voluntary Exercise in Alzheimer’s Disease. J. Neuroinflammation 2020, 17, 271. [Google Scholar] [CrossRef] [PubMed]
- Leardini-Tristão, M.; Andrade, G.; Garcia, C.; Reis, P.A.; Lourenço, M.; Moreira, E.T.S.; Lima, F.R.S.; Castro-Faria-Neto, H.C.; Tibirica, E.; Estato, V. Physical Exercise Promotes Astrocyte Coverage of Microvessels in a Model of Chronic Cerebral Hypoperfusion. J. Neuroinflammation 2020, 17, 117. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shen, K.; Liu, X.; Chen, D.; Chang, J.; Zhang, Y.; Kou, X. Voluntary Wheel-Running Exercise Attenuates Brain Aging of Rats through Activating MiR-130a-Mediated Autophagy. Brain Res. Bull. 2021, 172, 203–211. [Google Scholar] [CrossRef]
- Kwon, I.; Jang, Y.; Lee, Y. Endurance Exercise-Induced Autophagy/Mitophagy Coincides with a Reinforced Anabolic State and Increased Mitochondrial Turnover in the Cortex of Young Male Mouse Brain. J. Mol. Neurosci. 2021, 71, 42–54. [Google Scholar] [CrossRef]
- Chen, D.; Zhang, Y.; Zhang, M.; Chang, J.; Zeng, Z.; Kou, X.; Chen, N. Exercise Attenuates Brain Aging by Rescuing Down-Regulated Wnt/β-Catenin Signaling in Aged Rats. Front. Aging Neurosci. 2020, 12, 105. [Google Scholar] [CrossRef] [Green Version]
- Ahlskog, J.E. Aerobic Exercise: Evidence for a Direct Brain Effect to Slow Parkinson Disease Progression. Mayo Clin. Proc. 2018, 93, 360–372. [Google Scholar] [CrossRef] [Green Version]
- Sacheli, M.A.; Neva, J.L.; Lakhani, B.; Murray, D.K.; Vafai, N.; Shahinfard, E.; English, C.; McCormick, S.; Dinelle, K.; Neilson, N.; et al. Exercise Increases Caudate Dopamine Release and Ventral Striatal Activation in Parkinson’s Disease. Mov. Disord 2019, 34, 1891–1900. [Google Scholar] [CrossRef]
- Cicero, A.F.G.; Colletti, A. An Update on the Safety of Nutraceuticals and Effects on Lipid Parameters. Expert Opin. Drug Saf. 2018, 17, 303–313. [Google Scholar] [CrossRef]
- Espín, J.C.; García-Conesa, M.T.; Tomás-Barberán, F.A. Nutraceuticals: Facts and Fiction. Phytochemistry 2007, 68, 2986–3008. [Google Scholar] [CrossRef] [PubMed]
- Singh, R.B.; Watson, R.R.; Takahashi, T. (Eds.) The Role of Functional Food Security in Global Health; Academic Press: London, UK; San Diego, CA, USA, 2019; ISBN 978-0-12-813148-0. [Google Scholar]
- Das, L.; Bhaumik, E.; Raychaudhuri, U.; Chakraborty, R. Role of Nutraceuticals in Human Health. J. Food Sci. Technol. 2012, 49, 173–183. [Google Scholar] [CrossRef] [PubMed]
- Cencic, A.; Chingwaru, W. The Role of Functional Foods, Nutraceuticals, and Food Supplements in Intestinal Health. Nutrients 2010, 2, 611–625. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, Y.; Xu, D. Effects of Aerobic Exercise on Lipids and Lipoproteins. Lipids Health Dis. 2017, 16, 132. [Google Scholar] [CrossRef] [PubMed]
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Scarfò, G.; Piccarducci, R.; Daniele, S.; Franzoni, F.; Martini, C. Exploring the Role of Lipid-Binding Proteins and Oxidative Stress in Neurodegenerative Disorders: A Focus on the Neuroprotective Effects of Nutraceutical Supplementation and Physical Exercise. Antioxidants 2022, 11, 2116. https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11112116
Scarfò G, Piccarducci R, Daniele S, Franzoni F, Martini C. Exploring the Role of Lipid-Binding Proteins and Oxidative Stress in Neurodegenerative Disorders: A Focus on the Neuroprotective Effects of Nutraceutical Supplementation and Physical Exercise. Antioxidants. 2022; 11(11):2116. https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11112116
Chicago/Turabian StyleScarfò, Giorgia, Rebecca Piccarducci, Simona Daniele, Ferdinando Franzoni, and Claudia Martini. 2022. "Exploring the Role of Lipid-Binding Proteins and Oxidative Stress in Neurodegenerative Disorders: A Focus on the Neuroprotective Effects of Nutraceutical Supplementation and Physical Exercise" Antioxidants 11, no. 11: 2116. https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11112116