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KMID : 0921620140440010102
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Journal of Bacteriology and Virology
2014 Volume.44 No. 1 p.102 ~ p.107
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HIV-1 Tat Protein Promotes Amyloid β Generation and Tau Phosphorylation in Rat Hippocampal Slices
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Lee Eun-Ok
Jhang Kyoung-A
An Ye-Won
Ju Woong
Chong Young-Hae
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Abstract
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HIV-1 Tat protein has been implicated as a causative agent in the pathogenesis of HIV-1-associated neurocognitive disorder (HAND) and Alzheimer’s disease (AD)-like pathology in HIV-1 infected patients. Here, we provide insights into the potential roles of extracellular HIV-1 Tat protein in amyloid β (Aβ) generation and Tau phosphorylation, two major neuropathological features of AD. Exposure of the rat hippocampal slices to the full-length HIV-1 Tat protein (Tat1-86) for 3 days led to the increased levels of Aβ precursor protein (APP) accumulation, which accompanied by Aβ generation in the hippocampus, the brain region most commonly damaged in HIV-1-associated dementia (HAD). Moreover, extracellular HIV-1 Tat significantly stimulated the level of phosphrylated Tau (pTau) identified using immunoblotting with AT8 antibody, which recognizes abnormally hyperphosphorylated Tau. Collectively, our data suggest that HIV-1 Tat plays important roles in increasing the levels of APP accumulation, Aβ generation and Tau phosphorylation in the hippocampus, and thereby might contribute to the development of AD-like pathology in HIV-1-infected patients.
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KEYWORD
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HIV-1-associated neurocognitive disorder, HIV-1 Tat, pTau, Aβ, Hippocampus, Alzheimer’s disease
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