Abstract
BackgroundHIV-1 viral protein Tat partially mediates the neural dysfunction and neuronal cell death associated with HIV-1 induced neurodegeneration and neurocognitive disorders. Soy isoflavones provide protection against various neurotoxic insults to maintain neuronal function and thus help preserve neurocognitive capacity.Methodology/Principal FindingsWe demonstrate in primary cortical cell cultures that 17β-estradiol or isoflavones (genistein or daidzein) attenuate Tat1–86-induced expression of apoptotic proteins and subsequent cell death. Exposure of cultured neurons to the estrogen receptor antagonist ICI 182,780 abolished the anti-apoptotic actions of isoflavones. Use of ERα or ERβ specific antagonists determined the involvement of both ER isoforms in genistein and daidzein inhibition of caspase activity; ERβ selectively mediated downregulation of mitochondrial pro-apoptotic protein Bax. The findings suggest soy isoflavones effectively diminished HIV-1 Tat-induced apoptotic signaling.Conclusions/SignificanceCollectively, our results suggest that soy isoflavones represent an adjunctive therapeutic option with combination anti-retroviral therapy (cART) to preserve neuronal functioning and sustain neurocognitive abilities of HIV-1 infected persons.
Highlights
HIV-1 infection of the central nervous system (CNS) causes several neurological disorders, known as HIV-associated neurocognitive disorders (HAND) [1]
Conclusions/Significance: Collectively, our results suggest that soy isoflavones represent an adjunctive therapeutic option with combination anti-retroviral therapy to preserve neuronal functioning and sustain neurocognitive abilities of HIV1 infected persons
We investigated whether treatment with soy isoflavones, genistein or daidzein, could attenuate HIV-1 Tat-induced mitochondria associated apoptosis in cortical cell cultures
Summary
HIV-1 infection of the central nervous system (CNS) causes several neurological disorders, known as HIV-associated neurocognitive disorders (HAND) [1]. The continued prevalence of neurological dysfunction suggests cART fails to provide complete protection from the development of HAND [1,3,4] and there currently are no pharmacotherapies targeted to HAND. The observations that the viral regulatory protein Tat is actively secreted by infected cells, and that Tat mRNA is elevated in patients with HIV-1 suggest a possible role of extracellular Tat in the progression of HIV-1-induced neurodegeneration [23,24,25]. HIV-1 viral protein Tat partially mediates the neural dysfunction and neuronal cell death associated with HIV-1 induced neurodegeneration and neurocognitive disorders. Soy isoflavones provide protection against various neurotoxic insults to maintain neuronal function and help preserve neurocognitive capacity
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have