Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration. uri icon

Overview

abstract

  • CHCHD10 is mutated in rare cases of FTD and ALS and aggregates in mouse models of disease. Here we show that the disordered N-terminal domain of CHCHD10 forms amyloid fibrils and report their cryoEM structure. Disease-associated mutations cannot be accommodated by the WT fibril structure, while sequence differences between CHCHD10 and CHCHD2 are tolerated, explaining the co-aggregation of the two proteins and linking CHCHD10 and CHCHD2 amyloid fibrils to neurodegeneration.

publication date

  • July 22, 2024

Identity

PubMed Central ID

  • PMC11291021

Digital Object Identifier (DOI)

  • 10.1101/2024.07.18.604174

PubMed ID

  • 39091724