Thorase deficiency causes both Aβ accumulation and tau hyperphosphorylation in mouse brain

Area of Science:

• Neuroscience
• Molecular Biology
• Pathology

Background:

• Alzheimer's disease (AD) pathogenesis involves amyloid beta (Aβ) accumulation and hyperphosphorylated tau.
• The precise mechanisms driving these pathological hallmarks remain incompletely understood.

Purpose of the Study:

• To investigate the role of Thorase in the pathogenesis of Alzheimer's disease.
• To explore Thorase as a potential therapeutic target for AD.

Main Methods:

• Western blot and immunofluorescence staining in Thorase conditional knockout/transgenic mice.
• Co-immunoprecipitation assays to identify Thorase-interacting proteins.

Main Results:

• Thorase deletion promoted Aβ accumulation and tau hyperphosphorylation.
• Thorase regulated tau phosphorylation via protein phosphatase 2B (PP2B).
• Thorase deficiency impaired microglial phagocytosis and induced NLRP3 inflammasome-mediated neuroinflammation.

Conclusions:

• Thorase plays a critical role in modulating AD-related pathology.
• Thorase deficiency exacerbates neuroinflammation and protein aggregation.
• Thorase represents a potential druggable target for Alzheimer's disease and other neurodegenerative disorders.