Document Detail


Adjunctive therapies for HIV-1 associated neurologic disease.
MedLine Citation:
PMID:  16260393     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the past decade we have seen a milder phenotype and decreased incidence of HIV-1 associated dementia (HAD), largely due to the widespread use of combination chemotherapy to reduce viral burden. However, the prevalence of neurologic disease in people living with HIV-1 has actually increased, raising significant concerns that new therapeutic strategies, directed at restoring neuronal and glial homeostasis and signaling in the central nervous system (CNS), as opposed to directly interfering with the life cycle of HIV-1, must be developed. In this review, we focus briefly on previous Phase 1 clinical trials for adjunctive (i.e., chemotherapeutic agents that do not have a primary antiretroviral mechanism of action) therapy in patients with HAD, followed by an overview of key molecular events in the neuropathogenesis of HAD, and then discuss in more detail our rationale for investigating the effects of therapeutic agents that restore impaired mitochondrial bioenergetics in the CNS. Specifically, we focus on agents that either work in part through K-ATP channels, present in both mitochondria and plasma membranes, and agents that work to weakly uncouple the respiratory capacity of the electron transport chain in mitochondria from ATP production. We propose these agents may be complementary to currently available antiretroviral agents and may significantly improve the capacity of CNS infected with HIV-1 to meet increased bioenergetic demands involved in normal synaptic communication.
Authors:
S W Perry; J P Norman; H A Gelbard
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Neurotoxicity research     Volume:  8     ISSN:  1029-8428     ISO Abbreviation:  Neurotox Res     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-11-01     Completed Date:  2006-02-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100929017     Medline TA:  Neurotox Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  161-6     Citation Subset:  IM    
Affiliation:
Center for Aging and Developmental Biology, Kornberg Medical Research Institute, Rochester, NY 14642, USA.
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MeSH Terms
Descriptor/Qualifier:
AIDS Dementia Complex / drug therapy*,  metabolism
Animals
Antiretroviral Therapy, Highly Active
Energy Metabolism / drug effects
HIV-1*
Humans
Neuroprotective Agents / therapeutic use*
Grant Support
ID/Acronym/Agency:
AI49815/AI/NIAID NIH HHS; EHS07026/EH/NCEH CDC HHS; MH071176/MH/NIMH NIH HHS; MH56838/MH/NIMH NIH HHS; MH64570/MH/NIMH NIH HHS; NS31492/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Neuroprotective Agents

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