Journal
COMMUNICATIONS BIOLOGY
Volume 5, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-022-03343-7
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Funding
- Faculty Summer Research Fellowship from The University of Akron
- [NSF-CBET-2107619]
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This study reveals a potential crosstalk between Alzheimer's Disease (AD) and HIV/AIDS through the cross-seeding interactions between Aβ and SEVI proteins. The cross-seeding of SEVI with Aβ can prevent Aβ aggregation, reduce Aβ-induced cell toxicity, and attenuate Aβ-accumulated paralysis in transgenic AD C. elegans.
Cross-seeding of SEVI, a protein that enhances the infectivity of HIV virus, with Amyloid-beta (A beta) can prevent A beta aggregation, disaggregate preformed A beta fibrils, reduce A beta-induced cell toxicity, and attenuate A beta-accumulated paralysis in a transgenic C. elegans model of Alzheimer's Disease. Amyloid-beta (A beta) and semen-derived enhancer of viral infection (SEVI) are considered as the two causative proteins for central pathogenic cause of Alzheimer's disease (AD) and HIV/AIDS, respectively. Separately, A beta-AD and SEVI-HIV/AIDS systems have been studied extensively both in fundamental research and in clinical trials. Despite significant differences between A beta-AD and SEVI-HIV/AIDS systems, they share some commonalities on amyloid and antimicrobial characteristics between A beta and SEVI, there are apparent overlaps in dysfunctional neurological symptoms between AD and HIV/AIDS. Few studies have reported a potential pathological link between A beta-AD and SEVI-HIV/AIDS at a protein level. Here, we demonstrate the cross-seeding interactions between A beta and SEVI proteins using in vitro and in vivo approaches. Cross-seeding of SEVI with A beta enabled to completely prevent A beta aggregation at sub-stoichiometric concentrations, disaggregate preformed A beta fibrils, reduce A beta-induced cell toxicity, and attenuate A beta-accumulated paralysis in transgenic AD C. elegans. This work describes a potential crosstalk between AD and HIV/AIDS via the cross-seeding between A beta and SEVI, identifies SEVI as A beta inhibitor for possible treatment or prevention of AD, and explains the role of SEVI in the gender difference in AD.
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