Spatial transcriptomics analysis uncovers ER stress in MANF-deficient Purkinje cells underlying alcohol-induced cerebellar neurodegeneration in mice.

ABSTRACT: Alcohol use disorders (AUD) is one of the most prevalent mental disorders in the United States affecting more than 10% of the adult population. Cerebellar atrophy and Purkinje cell (PC) degeneration are frequently observed in patients with AUD. Alcohol can cause endoplasmic reticulum (ER) stress in PCs and alter PC structure and function. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress inducible protein highly expressed in PCs. It is neuroprotective in various ER stress-related pathological conditions. However, it is unknown whether MANF plays a role in protecting PCs from alcohol-induced ER stress and neurodegeneration. In this study, we generated PC-specific MANF knockout (KO) mouse model to test the hypothesis that MANF-deficient PCs are more susceptible to al

SUBMITTER: Wen W 

PROVIDER: S-EPMC12781712 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature