The mouse nicotinamide mononucleotide adenylyltransferase chaperones diverse pathological amyloid client proteins.

ABSTRACT: Molecular chaperones safeguard cellular protein homeostasis and obviate proteotoxicity. In the process of aging, as chaperone networks decline, aberrant protein amyloid aggregation accumulates in a mechanism that underpins neurodegeneration, leading to pathologies such as Alzheimer's disease and Parkinson's disease. Thus, it is important to identify and characterize chaperones for preventing such protein aggregation. In this work, we identified that the NAD⁺ synthase-nicotinamide mononucleotide adenylyltransferase (NMNAT) 3 from mouse (mN3) exhibits potent chaperone activity to antagonize aggregation of a wide spectrum of pathological amyloid client proteins including α-synuclein, Tau (K19), amyloid β, and islet amyloid polypeptide. By combining NMR spectroscopy, cross-linking m

SUBMITTER: Huang C 

PROVIDER: S-EPMC9108885 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature