Sirtuins Modulation: A Promising Strategy for HIV-Associated Neurocognitive Impairments

HIV-Associated neurocognitive disorder (HAND) is one of the major concerns since it persists in 40% of this population. Nowadays, HAND neuropathogenesis is considered to be caused by the infected cells that cross the brain-blood barrier and produce viral proteins that can be secreted and internalized into neurons leading to disruption of cellular processes. The evidence points to viral proteins such as Tat as the causal agent for neuronal alteration and thus HAND. The hallmarks in Tat-induced neurodegeneration are endoplasmic reticulum stress and mitochondrial dysfunction. Sirtuins (SIRTs) are NAD+-dependent deacetylases involved in mitochondria biogenesis, unfolded protein response, and intrinsic apoptosis pathway. Tat interaction with these deacetylases causes inhibition of SIRT1 and SIRT3. Studies revealed that SIRTs activation promotes neuroprotection in neurodegenerative diseases such Alzheimer's and Parkinson's disease. Therefore, this review focuses on Tat-induced neurotoxicity mechanisms that involve SIRTs as key regulators and their modulation as a therapeutic strategy for tackling HAND and thereby improving the quality of life of people living with HIV.

Automated summary

HIV-associated neurocognitive disorder (HAND) is a significant concern, affecting 40% of the population. Recent research has shown that the viral protein Tat is responsible for neuronal alteration, leading to endoplasmic reticulum stress and mitochondrial dysfunction. Activation of SIRTs has been found to promote neuroprotection in neurodegenerative diseases such as Alzheimer's and Parkinson's disease.