Creatine Protects Against Mitochondrial Dysfunction Associated with HIV-1 Tat-Induced Neuronal Injury

Title:Creatine Protects Against Mitochondrial Dysfunction Associated with HIV-1 Tat-Induced Neuronal Injury

Volume: 12 Issue: 6

Author(s): Patrick R. Stevens, Jeremy W. Gawryluk, Liang Hui, Xuesong Chen and Jonathan D. Geiger

Affiliation:

Keywords: Creatine, HIV-1 associated neurocognitive disorders, HIV-1 Tat, mitochondria dysfunction, neuroprotection.

Abstract: HIV-1 infected individuals live longer but experience a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells lead to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat_1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1

Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND.

Cite this article as:

Stevens R. Patrick, Gawryluk W. Jeremy, Hui Liang, Chen Xuesong and Geiger D. Jonathan, Creatine Protects Against Mitochondrial Dysfunction Associated with HIV-1 Tat-Induced Neuronal Injury, Current HIV Research 2014; 12 (6) . https://dx.doi.org/10.2174/1570162X13666150121101544