Abstract
Parkinson’s disease (PD) is one of the most common progressive neurodegenerative disorders in modern society. The disease involves many genetic risk factors as well as a sporadic pathogenesis that is age- and environment-dependent. Of particular interest is the formation of intra-neural fibrillar aggregates, namely Lewy bodies (LBs), the histological hallmark of PD, which results from aberrant protein homeostasis or misfolding that results in neurotoxicity. A better understanding of the molecular mechanism and composition of these cellular inclusions will help shed light on the progression of misfolding-associated neurodegenerative disorders. Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is found to co-aggregate with α-synuclein (αS), the major component of LBs. Several familial mutations of UCH-L1, namely p.Ile93Met (p.I93M), p.Glu7Ala (p.E7A), and p.Ser18Tyr (p.S18Y), are associated with PD and other neurodegenerative disorders. Here, we review recent progress and recapitulate the impact of PD-associated mutations of UCH-L1 in the context of their biological functions gleaned from biochemical and biophysical studies. Finally, we summarize the effect of these genetic mutations and post-translational modifications on the association of UCHL1 and PD in terms of loss of cellular functions or gain of cellular toxicity.
Keywords: UCH-L1, α-synuclein, Lewy bodies, Parkinson’s disease, ubiquitin, misfolding.
Current Protein & Peptide Science
Title:Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson's Disease and Neurodegenerative Disorders
Volume: 18 Issue: 7
Author(s): Yun-Tzai C. Lee and Shang-Te D. Hsu*
Affiliation:
- Institute of Biological Chemistry, Academia Sinica, 128, Section 2, Academia Road, Aipei, 11529,Taiwan,Taiwan
Keywords: UCH-L1, α-synuclein, Lewy bodies, Parkinson’s disease, ubiquitin, misfolding.
Abstract: Parkinson’s disease (PD) is one of the most common progressive neurodegenerative disorders in modern society. The disease involves many genetic risk factors as well as a sporadic pathogenesis that is age- and environment-dependent. Of particular interest is the formation of intra-neural fibrillar aggregates, namely Lewy bodies (LBs), the histological hallmark of PD, which results from aberrant protein homeostasis or misfolding that results in neurotoxicity. A better understanding of the molecular mechanism and composition of these cellular inclusions will help shed light on the progression of misfolding-associated neurodegenerative disorders. Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is found to co-aggregate with α-synuclein (αS), the major component of LBs. Several familial mutations of UCH-L1, namely p.Ile93Met (p.I93M), p.Glu7Ala (p.E7A), and p.Ser18Tyr (p.S18Y), are associated with PD and other neurodegenerative disorders. Here, we review recent progress and recapitulate the impact of PD-associated mutations of UCH-L1 in the context of their biological functions gleaned from biochemical and biophysical studies. Finally, we summarize the effect of these genetic mutations and post-translational modifications on the association of UCHL1 and PD in terms of loss of cellular functions or gain of cellular toxicity.
Export Options
About this article
Cite this article as:
Lee C. Yun-Tzai and Hsu D. Shang-Te*, Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson's Disease and Neurodegenerative Disorders, Current Protein & Peptide Science 2017; 18 (7) . https://dx.doi.org/10.2174/1389203717666160217143721
DOI https://dx.doi.org/10.2174/1389203717666160217143721 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Vitamin E - Occurrence, Biosynthesis by Plants and Functions in Human Nutrition
Mini-Reviews in Medicinal Chemistry Potential Anti-inflammatory Effects of Hesperidin from the Genus Citrus
Current Medicinal Chemistry High Content, Multi-Parameter Analyses in Buccal Cells to Identify Alzheimer’s Disease
Current Alzheimer Research Therapeutic Targets for the Management of Peripheral Nerve Injury- Induced Neuropathic Pain
CNS & Neurological Disorders - Drug Targets Innovative Anthocyanin/Anthocyanidin Formulation Protects SK-N-SH Cells Against the Amyloid-β Peptide-Induced Toxicity: Relevance to Alzheimer’s Disease
Central Nervous System Agents in Medicinal Chemistry Heat Shock Proteins: Mediators of Atherosclerotic Development
Current Drug Targets AMPK Regulation of Glucose, Lipid and Protein Metabolism: Mechanisms and Nutritional Significance
Current Protein & Peptide Science VEGF-VEGFR System as a Target for Suppressing Inflammation and other Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Induced Pluripotent Stem Cells in Regenerative Medicine and Disease Modeling
Current Stem Cell Research & Therapy Molecular Hydrogen Application in Stroke: Bench to Bedside
Current Pharmaceutical Design Arachidonic Acid Metabolites in Neurologic Disorders
CNS & Neurological Disorders - Drug Targets Small Molecule Antagonists of the Chemokine Receptor CCR5
Current Topics in Medicinal Chemistry Novel Approaches for Potential Therapy of Cystic Fibrosis
Current Drug Targets CXXC5 Associates with Smads to Mediate TNF-α Induced Apoptosis
Current Molecular Medicine Senescence of the Brain: Focus on Cognitive Kinases
Current Pharmaceutical Design Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review
Drug Delivery Letters Differences Between Parkinson’s and Huntington’s Diseases and Their Role for Prioritization of Stem Cell-Based Treatments
Current Molecular Medicine Nonhuman Primate Models of Alzheimer-Like Cerebral Proteopathy
Current Pharmaceutical Design New Proposals for Treatment Sporadic Alzheimers Disease
Central Nervous System Agents in Medicinal Chemistry Potential Drugs and Methods for Preventing or Delaying the Progression of Huntington's Disease
Recent Patents on CNS Drug Discovery (Discontinued)