The UNC5C T835M mutation associated with Alzheimer's disease leads to neurodegeneration involving oxidative stress and hippocampal atrophy in aged mice.

ABSTRACT: Alzheimer's disease (AD) is characterized by amyloid plaques, neurofibrillary tangles, and synaptic and neuronal loss. Recently, a rare autosomal dominant coding mutation, T835M, in the Un-coordinated 5c (UNC5C) netrin receptor gene was segregated with late-onset AD (LOAD). Overexpression of T835M in primary hippocampal neurons increased cell death in response to neurotoxic stimuli including beta-amyloid (Aβ) suggesting a mechanism by which T835M may confer increased risk of LOAD. However, the molecular mechanism of T835M-mediated cell death remained under explored. Toward this end, we generated a mouse T835M knock-in (Unc5c^KI/KI) model and employed biochemical and histological analyses to understand the molecular mechanism of T835M-mediated pathogenesis in late onset Alzheimer'

SUBMITTER: Karunakaran DKP 

PROVIDER: S-EPMC12135551 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature