Next Article in Journal
Quantitative Prediction of Solvation Free Energy in Octanol of Organic Compounds
Next Article in Special Issue
Physiological and Pathological Role of Alpha-synuclein in Parkinson’s Disease Through Iron Mediated Oxidative Stress; The Role of a Putative Iron-responsive Element
Previous Article in Journal
Importance of Translational Entropy of Water in Biological Self-Assembly Processes like Protein Folding
Previous Article in Special Issue
Neuropathology and Therapeutic Intervention in Spinal and Bulbar Muscular Atrophy
Article Menu

Export Article

Open AccessReview
Int. J. Mol. Sci. 2009, 10(3), 1045-1063;

Molecular Pathology of Neuro-AIDS (CNS-HIV)

Department of Pathology, University of California, San Diego / 9500 Gilman Dr. La Jolla, CA 92093, U.S.A.;
Department of Neurosciences, University of California, San Diego / 9500 Gilman Dr. La Jolla, CA 92093, U.S.A
Department of Psychiatry, University of California, San Diego / 9500 Gilman Dr. La Jolla, CA 92093, U.S.A
Author to whom correspondence should be addressed.
Received: 9 February 2009 / Revised: 5 March 2009 / Accepted: 9 March 2009 / Published: 11 March 2009
(This article belongs to the Special Issue Advances in Molecular Neuropathology)
Full-Text   |   PDF [655 KB, uploaded 19 June 2014]


The cognitive deficits in patients with HIV profoundly affect the quality of life of people living with this disease and have often been linked to the neuro-inflammatory condition known as HIV encephalitis (HIVE). With the advent of more effective anti-retroviral therapies, HIVE has shifted from a sub-acute to a chronic condition. The neurodegenerative process in patients with HIVE is characterized by synaptic and dendritic damage to pyramidal neurons, loss of calbindin-immunoreactive interneurons and myelin loss. The mechanisms leading to neurodegeneration in HIVE might involve a variety of pathways, and several lines of investigation have found that interference with signaling factors mediating neuroprotection might play an important role. These signaling pathways include, among others, the GSK3b, CDK5, ERK, Pyk2, p38 and JNK cascades. Of these, GSK3b has been a primary focus of many previous studies showing that in infected patients, HIV proteins and neurotoxins secreted by immune-activated cells in the brain abnormally activate this pathway, which is otherwise regulated by growth factors such as FGF. Interestingly, modulation of the GSK3b signaling pathway by FGF1 or GSK3b inhibitors (lithium, valproic acid) is protective against HIV neurotoxicity, and several pilot clinical trials have demonstrated cognitive improvements in HIV patients treated with GSK3b inhibitors. In addition to the GSK3b pathway, the CDK5 pathway has recently been implicated as a mediator of neurotoxicity in HIV, and HIV proteins might activate this pathway and subsequently disrupt the diverse processes that CDK5 regulates, including synapse formation and plasticity and neurogenesis. Taken together, the GSK3b and CDK5 signaling pathways are important regulators of neurotoxicity in HIV, and modulation of these factors might have therapeutic potential in the treatment of patients suffering from HIVE. In this context, the subsequent sections will focus on reviewing the involvement of the GSK3b and CDK5 pathways in neurodegeneration in HIV. View Full-Text
Keywords: HIV; encephalitis; NeuroAIDS; inflammation; GSK3β; CDK5 HIV; encephalitis; NeuroAIDS; inflammation; GSK3β; CDK5
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

MDPI and ACS Style

Crews, L.; Patrick, C.; Achim, C.L.; Everall, I.P.; Masliah, E. Molecular Pathology of Neuro-AIDS (CNS-HIV). Int. J. Mol. Sci. 2009, 10, 1045-1063.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top