HIV-1 protein-mediated amyloidogenesis in rat hippocampal cell cultures.
Since the beginning of the highly active antiretroviral therapy (HAART) era, epidemiological evidence indicates an increasing incidence of Alzheimer's (AD)-like brain pathology in aging HIV patients. Emerging evidence warns of potential convergent mechanisms underlying HIV- and Abeta-mediated neurodegeneration. We found that HIV-1 Tat B and gp120 promote the secretion of Abeta 1-42 in primary rat fetal hippocampal cell cultures. Our results demonstrate that the variant of Tat expressed by the neurotropic subtype of HIV-1 virus (HIV-1 clade B) specifically induces both the release of amyloidogenic Abeta 1-42 and the accumulation of cell-bound amyloid aggregates. The results of the research rationalize testing of the ability of beta-amyloid aggregation inhibitors to attenuate HIV protein-mediated cognitive deficits in animal models of NeuroAIDS. The long-term goal of the study is to evaluate the potential benefits of anti-amyloidogenic therapies for management of cognitive dysfunction in aging HIV-1 patients.
Aksenov
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Program in Behavioral Neuroscience, University of South Carolina, United States. aksenov@mailbox.sc.edu
Aksenova
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Mactutus
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D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology / Q000502:physiology*; D015497:HIV-1; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology / Q000502:physiology*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C514793:gp120 protein, Human immunodeficiency virus 1; D054322:tat Gene Products, Human Immunodeficiency Virus