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
-
Cerebrovascular Amyloidosis and Dementia
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Electroencephalography and Dementia: A Literature Review and Future Perspectives
CNS & Neurological Disorders - Drug Targets Immune Functions of Glia and Neurons in the Central Nervous System
Current Immunology Reviews (Discontinued) Developments in Imaging Technologies Related to Hypertensive Cardiovascular Diseases
Current Pharmaceutical Design A Palliative Care Approach to the Advanced Heart Failure Patient
Current Cardiology Reviews Advanced Glycation End Products, Oxidative Stress and Metalloproteinases are altered in the Cerebral Microvasculature during Aging
Current Neurovascular Research Anti-Amyloid Treatments in Alzheimers Disease
Recent Patents on CNS Drug Discovery (Discontinued) Tau Silencing by siRNA in the P301S Mouse Model of Tauopathy
Current Gene Therapy Age-related Changes in Pharmacodynamics: Focus on Drugs Acting on Central Nervous and Cardiovascular Systems
Current Drug Metabolism Endocannabinoid Regulation of Matrix Metalloproteinases: Implications in Ischemic Stroke
Cardiovascular & Hematological Agents in Medicinal Chemistry Lysosomal Storage Diseases and the Blood-Brain Barrier
Current Pharmaceutical Design Anticoagulation in Patients with Heparin-Induced Thrombocytopenia undergoing Percutaneous Coronary Angiography and Interventions
Current Pharmaceutical Design High PIB Retention in Alzheimers Disease is an Early Event with Complex Relationship with CSF Biomarkers and Functional Parameters
Current Alzheimer Research Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer’s Disease
Current Neuropharmacology Pathology Associated Memory Deficits in Swedish Mutant Genome-Based Amyloid Precursor Protein Transgenic Mice
Current Aging Science Neuroprotective Therapies for Alzheimers Disease
Current Pharmaceutical Design Reduction of β-Amyloid Accumulation by Reticulon 3 in Transgenic Mice
Current Alzheimer Research The Mechanistic Links Between Proteasome Activity, Aging and Agerelated Diseases
Current Genomics Small Molecule Inhibitors of NF-κB and JAK/STAT Signal Transduction Pathways as Promising Anti-Inflammatory Therapeutics
Mini-Reviews in Medicinal Chemistry Systems Biology Research into Cardiovascular Disease: Contributions of Lipidomics-based Approaches to Biomarker Discovery
Current Drug Discovery Technologies