Pilot Award Recipient: Valeria Avdoshina, MD, PhD

Human immunodeficiency virus (HIV) enters central nervous system (CNS) and causes synapto-dendritic simplification as well as motor and cognitive function alterations seen in a subset of HIV positive individuals even in the presence of antiretroviral therapy correlate with HIV-associated neurocognitive disorder (HAND). Yet, the molecular mechanisms leading to these neuropathological features are still not fully understood. HIV can affect the brain soon after infection and leads to encephalopathy. This proposal examines a new alternative mechanism of HIV neurotoxicity by focusing on a possible cause of synaptic simplification. In particular, the investigators will test the hypothesis that one of the main mechanisms of gp120 toxicity initiates when the viral protein binds to MTs and perhaps affect tubulin PTMs. To test this hypothesis the researchers propose to: examine the ability of gp120 to change MTs dynamics (Aim 1) and to examine the neuroprotective property of Helix-A peptide against gp120-mediated neurotoxicity in human neurons (Aim 2). Data from this proposal have the potential of providing new information about a novel therapy against HAND. Moreover, in the course of the proposed research, the investigators will obtain preliminary data for Dr. Avdoshina's first NIH R01 application.