Pharmacological targeting of mitophagy via ALT001 improves herpes simplex virus 1 (HSV1)-mediated microglial inflammation and promotes amyloid β phagocytosis by restricting HSV1 infection.

ABSTRACT: Rationale: One of the hallmarks of Alzheimer's disease (AD) is the accumulation of dysfunctional mitochondria. Herpes simplex virus type 1 (HSV1) may be a risk factor for the neuropathology linked to amyloid β (Aβ) accumulation. However, the mechanisms underlying HSV1-associated mitochondrial dysfunction in AD remain unclear. ALT001 is a novel drug that ameliorates AD-related cognitive impairment via ULK1/Rab9-mediated alternative mitophagy. In this study, we investigated the effects of ALT001 on the neurodegeneration-related microglial signatures associated with HSV1 infection. Methods: Molecular mechanisms and physiological functions of mitophagy was investigated in HSV1-infected microglia, including primary murine and human embryonic stem cell (ESC)-derived microglia (ES-M

SUBMITTER: Oh SJ 

PROVIDER: S-EPMC12036882 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature