Ketone bodies protection against HIV‐1 Tat‐induced neurotoxicity

摘要: HIV-1 associated neurocognitive disorder (HAND) is a syndrome that ranges clinically from subtle neuropsychological impairments to profoundly disabling HIV-associated dementia. Not only the pathogenesis of HAND unclear, but also effective treatments are unavailable. The transactivator transcription protein (HIV-1 Tat) strongly implicated in HAND, part, because its well-characterized ability directly excite neurons and cause neurotoxicity. Consistent with previous findings others, we demonstrate here Tat induced neurotoxicity, increased intracellular calcium, disrupted variety mitochondria functions, such as reducing mitochondrial membrane potential, increasing levels reactive oxygen species, decreasing bioenergetic efficiency. Of therapeutic importance, show treatment cultured ketone bodies normalized changes function, neuronal cell death. Ketone normally produced body serve alternative energy substrates tissues including brain can cross blood-brain barrier. Ketogenic strategies have been used for neurological disorders our current results suggest similar may provide clinical benefits HAND.