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 |

- 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
- Announcements
Related Articles
-
Effects of Estrogen in the Brain: Is it a Neuroprotective Agent in Alzheimers Disease?
Current Aging Science Intrinsically Disordered Domains, Amyloids and Protein Liquid Phases: Evolving Concepts and Open Questions
Protein & Peptide Letters Age-Related Neurodegeneration Prevention Through mTOR Inhibition: Potential Mechanisms and Remaining Questions
Current Topics in Medicinal Chemistry Treatment Approaches in Elderly Patients with Head and Neck Cancer
Anti-Cancer Agents in Medicinal Chemistry The Interactions Between Alzheimer’s Disease and Major Depression: Role of Ca<sup>2+</sup> Channel Blockers and Ca<sup>2+</sup>/cAMP Signalling
Current Drug Research Reviews Gene Therapy and Cell Reprogramming For the Aging Brain: Achievements and Promise
Current Gene Therapy Drugs and Aggression
Recent Patents on CNS Drug Discovery (Discontinued) Nano-constructed Carriers Loaded With Antioxidant: Boon For Cardiovascular System
Current Pharmaceutical Design Ameliorative Effects of Baicalein on an Amyloid-β Induced Alzheimer's Disease Rat Model: A Proteomics Study
Current Alzheimer Research Dorsal Stream Dysfunction in Children. A Review and an Approach to Diagnosis and Management
Current Pediatric Reviews Potential Application of Dietary Polyphenols from Red Wine to Attaining Healthy Ageing
Current Topics in Medicinal Chemistry Pyrrolo-isoxazole: A Key Molecule with Diverse Biological Actions
Mini-Reviews in Medicinal Chemistry Acetylcholinesterase (AChE) - Amyloid-β-Peptide Complexes in Alzheimers Disease. The Wnt Signaling Pathway
Current Alzheimer Research Impaired Translation of Spatial Representation in Young Onset Alzheimer’s Disease Patients
Current Alzheimer Research New Approaches for the Treatment of Mental Disorders Comorbid with Inflammatory Diseases
Current Topics in Medicinal Chemistry Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options
Current Neuropharmacology Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important Players
Current Topics in Medicinal Chemistry Role of Resveratrol and its Analogues in the Treatment of Neurodegenerative Diseases: Focus on Recent Discoveries
CNS & Neurological Disorders - Drug Targets Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview
Current Medicinal Chemistry Prevalence, Incidence, Risk and Protective Factors of Amnestic Mild Cognitive Impairment in the Elderly in Shanghai
Current Alzheimer Research