GSK3-ARC/Arg3.1 and GSK3-Wnt signaling axes trigger amyloid-β accumulation and neuroinflammation in middle-aged Shugoshin 1 mice.

ABSTRACT: The cerebral amyloid-β accumulation that begins in middle age is considered the critical triggering event in the pathogenesis of late-onset Alzheimer's disease (LOAD). However, the molecular mechanism remains elusive. The Shugoshin 1 (Sgo1^-/+ ) mouse model, a model for mitotic cohesinopathy-genomic instability that is observed in human AD at a higher rate, showed spontaneous accumulation of amyloid-β in the brain at old age. With the model, novel insights into the molecular mechanism of LOAD development are anticipated. In this study, the initial appearance of cerebral amyloid-β accumulation was determined as 15-18 months of age (late middle age) in the Sgo1^-/+ model. The amyloid-β accumulation was associated with unexpected GSK3α/β inactivation, Wnt signaling activat

SUBMITTER: Rao CV 

PROVIDER: S-EPMC7576275 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature