Abstract
HIV-1 Tat protein has been shown to have a crucial role in HIV-1-associated neurocognitive disorders (HAND), which includes a group of syndromes ranging from undetectable neurocognitive impairment to dementia. The abuse of psychostimulants, such as cocaine, by HIV infected individuals, may accelerate and intensify neurological damage. On the other hand, exposure to Tat potentiates cocaine-mediated reward mechanisms, which further promotes HAND. Here, we show that didehydro-Cortistatin A (dCA), an analog of a natural steroidal alkaloid, crosses the blood-brain barrier, cross-neutralizes Tat activity from several HIV-1 clades and decreases Tat uptake by glial cell lines. In addition, dCA potently inhibits Tat mediated dysregulation of IL-1β, TNF-α and MCP-1, key neuroinflammatory signaling proteins. Importantly, using a mouse model where doxycycline induces Tat expression, we demonstrate that dCA reverses the potentiation of cocaine-mediated reward. Our results suggest that adding a Tat inhibitor, such as dCA, to current antiretroviral therapy may reduce HIV-1-related neuropathogenesis.
Keywords: Cocaine, conditioned place preference, didehydro-Cortistatin A, HAND, HIV-1, neuroinflammation, reward, Tat.
Current HIV Research
Title:Didehydro-Cortistatin A Inhibits HIV-1 Tat Mediated Neuroinflammation and Prevents Potentiation of Cocaine Reward in Tat Transgenic Mice
Volume: 13 Issue: 1
Author(s): Sonia Mediouni, Joseph Jablonski, Jason J. Paris, Mark A. Clementz, Suzie Thenin-Houssier, Jay P. McLaughlin and Susana T. Valente
Affiliation:
Keywords: Cocaine, conditioned place preference, didehydro-Cortistatin A, HAND, HIV-1, neuroinflammation, reward, Tat.
Abstract: HIV-1 Tat protein has been shown to have a crucial role in HIV-1-associated neurocognitive disorders (HAND), which includes a group of syndromes ranging from undetectable neurocognitive impairment to dementia. The abuse of psychostimulants, such as cocaine, by HIV infected individuals, may accelerate and intensify neurological damage. On the other hand, exposure to Tat potentiates cocaine-mediated reward mechanisms, which further promotes HAND. Here, we show that didehydro-Cortistatin A (dCA), an analog of a natural steroidal alkaloid, crosses the blood-brain barrier, cross-neutralizes Tat activity from several HIV-1 clades and decreases Tat uptake by glial cell lines. In addition, dCA potently inhibits Tat mediated dysregulation of IL-1β, TNF-α and MCP-1, key neuroinflammatory signaling proteins. Importantly, using a mouse model where doxycycline induces Tat expression, we demonstrate that dCA reverses the potentiation of cocaine-mediated reward. Our results suggest that adding a Tat inhibitor, such as dCA, to current antiretroviral therapy may reduce HIV-1-related neuropathogenesis.
Export Options
About this article
Cite this article as:
Mediouni Sonia, Jablonski Joseph, Paris J. Jason, Clementz A. Mark, Thenin-Houssier Suzie, McLaughlin P. Jay and Valente T. Susana, Didehydro-Cortistatin A Inhibits HIV-1 Tat Mediated Neuroinflammation and Prevents Potentiation of Cocaine Reward in Tat Transgenic Mice, Current HIV Research 2015; 13 (1) . https://dx.doi.org/10.2174/1570162X13666150121111548
DOI https://dx.doi.org/10.2174/1570162X13666150121111548 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
Call for Papers in Thematic Issues
Management of HIV: Management of HIV: old challenges and new needs
The aim of this thematic issue is to provide the most recent updates regarding the effective management of HIV infection. Antiretroviral therapy (ART) has significantly decreased HIV-related mortality, leading to an enhancement in the quality of life and life expectancy for people living with HIV (PLWH). Despite the numerous advancements ...read more
- 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
-
Novel Therapeutic Strategies for Dementia
CNS & Neurological Disorders - Drug Targets Biology and Therapeutic Applications of Peroxisome Proliferator- Activated Receptors
Current Topics in Medicinal Chemistry Editorial (Thematic Issue: Treating Major Age-Related Diseases in Older and Oldest Old Patients)
Current Pharmaceutical Design Cognitive Impairment with Vascular Impairment and Degeneration
Current Neurovascular Research Trajectories of Age-Related Cognitive Decline and Potential Associated Factors of Cognitive Function in Senior Citizens of Beijing
Current Alzheimer Research The Cytokine Network in HIV Infection
Current Molecular Medicine Editorial (Thematic Issue: The Link between Alzheimer’s Disease and Down Syndrome. A Historical Perspective)
Current Alzheimer Research NO to Breast: When, Why and Why Not?
Current Pharmaceutical Design Diagnostic and Prognostic Potential of Retinal Biomarkers in Early On-Set Alzheimer’s Disease
Current Alzheimer Research Radix Angelica Sinensis that Contains the Component Z-Ligustilide Promotes Adult Neurogenesis to Mediate Recovery from Cognitive Impairment
Current Neurovascular Research Targeting Heme Oxygenase-1 for Neuroprotection and Neuroinflammation in Neurodegenerative Diseases
Current Drug Targets Pitavastatin and 4-Hydroxy-3-Methoxyacetophenone (HMAP) Reduce Cognitive Dysfunction in Vascular Dementia During Experimental Diabetes
Current Neurovascular Research The Pentacyclic Triterpenoids in Herbal Medicines and Their Pharmacological Activities in Diabetes and Diabetic Complications
Current Medicinal Chemistry Increased CRMP2 Phosphorylation is Observed in Alzheimers Disease; Does this Tell us Anything About Disease Development?
Current Alzheimer Research On Chemical Structures with Potent Antiepileptic/Anticonvulsant Profile
Mini-Reviews in Medicinal Chemistry Pharmacotherapy for Obesity
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Impaired Translation of Spatial Representation in Young Onset Alzheimer’s Disease Patients
Current Alzheimer Research Herbal Medicine for Slowing Aging and Aging-associated Conditions: Efficacy, Mechanisms and Safety
Current Vascular Pharmacology Challenges in Neuronal Apoptosis
Current Alzheimer Research Obesity and Metabolic Syndrome Affect the Cholinergic Transmission a nd Cognitive Functions
CNS & Neurological Disorders - Drug Targets