Mistranslation-associated perturbations of proteostasis do not promote accumulation of amyloid beta and plaque deposition in aged mouse brain.

ABSTRACT: A common perception in age-related neurodegenerative diseases posits that a decline in proteostasis is key to the accumulation of neuropathogenic proteins, such as amyloid beta (Aβ), and the development of sporadic Alzheimer's disease (AD). To experimentally challenge the role of protein homeostasis in the accumulation of Alzheimer's associated protein Aβ and levels of associated Tau phosphorylation, we disturbed proteostasis in single APP knock-in mouse models of AD building upon Rps9 D95N, a recently identified mammalian ram mutation which confers heightened levels of error-prone translation together with an increased propensity for random protein aggregation and which is associated with accelerated aging. We crossed the Rps9 D95N mutation into knock-in mice expressing humanized Aβ with

SUBMITTER: Santhosh Kumar H 

PROVIDER: S-EPMC10682081 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature