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HSV-1 infection induces brain cofilin hyperphosphorylation in the 5xFAD Alzheimer's Disease mouse model

Gharavi-naeini, L.; Shu, Z.; Alem, F.; Feng, S.; Chilin, L. D.; Feng, P.; Wu, Y.

2025-08-12 microbiology
10.1101/2025.08.10.669568 bioRxiv
Show abstract

Alzheimers disease (AD) is a degenerative neurological disease characterized by various biological signatures, including synaptic dysfunction, {beta}-amyloid plaques, hyperphosphorylated Tau, cofilin-actin rods, and Hirano bodies, all of which are linked to the actin cytoskeleton and its regulators. Additionally, the presence of herpes simplex virus type 1 (HSV-1) in the brains of AD patients has long been suggested as a contributing factor for AD. However, mechanisms by which HSV-1 accelerates AD pathogenesis remain poorly understood. Here we report that HSV-1 infection induces hyperphosphorylation of cofilin in the brains of 5xFAD mice. Cofilin is an actin depolymerizing factor, and its S3 phosphorylation inactivates cofilins activity to depolymerize actin filaments. These findings facilitate the understanding of impacts of HSV-1 infection on the development of Alzheimers disease and have implications in AD therapeutics.

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