Global Proteotoxicity Caused by Human β₂ Microglobulin Variants Impairs the Unfolded Protein Response in C. elegans.

ABSTRACT: Aggregation of β₂ microglobulin (β₂m) into amyloid fibrils is associated with systemic amyloidosis, caused by the deposition of amyloid fibrils containing the wild-type protein and its truncated variant, ΔN6 β₂m, in haemo-dialysed patients. A second form of familial systemic amyloidosis caused by the β₂m variant, D76N, results in amyloid deposits in the viscera, without renal dysfunction. Although the folding and misfolding mechanisms of β₂ microglobulin have been widely studied in vitro and in vivo, we lack a comparable understanding of the molecular mechanisms underlying toxicity in a cellular and organismal environment. Here, we established transgenic C. elegans lines expressing wild-type (WT) human β₂m, or the two

SUBMITTER: Good SC 

PROVIDER: S-EPMC8509642 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature