HSV-1 infection induces brain cofilin hyperphosphorylation in the 5×FAD Alzheimer’s Disease mouse model

Alzheimer’s disease (AD) is a degenerative neurological disease characterized by various biological signatures, including synaptic dysfunction, β-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 5×FAD mice. Cofilin is an actin depolymerizing factor, and its S3 phosphorylation inactivates cofilin’s activity to depolymerize actin filaments. These findings facilitate the understanding of impacts of HSV-1 infection on the development of Alzheimer’s disease and have implications in AD therapeutics.

• Publication year

  2025

• Venue

  bioRxiv

• Publication date

  2025-08-12

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1101/2025.08.10.669568PMID 40832295PMCID 12363793
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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