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Caffeine Blocks HIV-1 Tat-Induced Amyloid Beta Production and Tau Phosphorylation.

ABSTRACT: The increased life expectancy of people living with HIV-1 who are taking effective anti-retroviral therapeutics is now accompanied by increased Alzheimer's disease (AD)-like neurocognitive problems and neuropathological features such as increased levels of amyloid beta (A?) and phosphorylated tau proteins. Others and we have shown that HIV-1 Tat promotes the development of AD-like pathology. Indeed, HIV-1 Tat once endocytosed into neurons can alter morphological features and functions of endolysosomes as well as increase A? generation. Caffeine has been shown to have protective actions against AD and based on our recent findings that caffeine can inhibit endocytosis in neurons and can prevent neuronal A? generation, we tested the hypothesis that caffeine blocks HIV-1 Tat-induced A? generation and tau phosphorylation. In SH-SY5Y cells over-expressing wild-type amyloid beta precursor protein (A?PP), we demonstrated that HIV-1 Tat significantly increased secreted levels and intracellular levels of A? as well as cellular protein levels of phosphorylated tau. Caffeine significantly decreased levels of secreted and cellular levels of A?, and significantly blocked HIV-1 Tat-induced increases in secreted and cellular levels of A?. Caffeine also blocked HIV-1 Tat-induced increases in cellular levels of phosphorylated tau. Furthermore, caffeine blocked HIV-1 Tat-induced endolysosome dysfunction as indicated by decreased protein levels of vacuolar-ATPase and increased protein levels of cathepsin D. These results further implicate endolysosome dysfunction in the pathogenesis of AD and HAND, and by virtue of its ability to prevent and/or block neuropathological features associated with AD and HAND caffeine might find use as an effective adjunctive therapeutic agent.

SUBMITTER: Soliman ML

PROVIDER: S-EPMC5316495 | biostudies-other | 2017 Mar

REPOSITORIES: biostudies-other

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Caffeine Blocks HIV-1 Tat-Induced Amyloid Beta Production and Tau Phosphorylation.

Soliman Mahmoud L ML Geiger Jonathan D JD Chen Xuesong X

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 20160915 1

The increased life expectancy of people living with HIV-1 who are taking effective anti-retroviral therapeutics is now accompanied by increased Alzheimer's disease (AD)-like neurocognitive problems and neuropathological features such as increased levels of amyloid beta (Aβ) and phosphorylated tau proteins. Others and we have shown that HIV-1 Tat promotes the development of AD-like pathology. Indeed, HIV-1 Tat once endocytosed into neurons can alter morphological features and functions of endolys ...[more]

PMID: 27629410

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Dataset Information

Caffeine Blocks HIV-1 Tat-Induced Amyloid Beta Production and Tau Phosphorylation.

Publications

Caffeine Blocks HIV-1 Tat-Induced Amyloid Beta Production and Tau Phosphorylation.

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