TDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP.

ABSTRACT: The abnormal assembly of TAR DNA-binding protein 43 (TDP-43) in neuronal and glial cells characterizes nearly all cases of amyotrophic lateral sclerosis (ALS) and around half of cases of frontotemporal lobar degeneration (FTLD)^1,2. A causal role for TDP-43 assembly in neurodegeneration is evidenced by dominantly inherited missense mutations in TARDBP, the gene encoding TDP-43, that promote assembly and give rise to ALS and FTLD^3-7. At least four types (A-D) of FTLD with TDP-43 pathology (FTLD-TDP) are defined by distinct brain distributions of assembled TDP-43 and are associated with different clinical presentations of frontotemporal dementia⁸. We previously showed, using cryo-electron microscopy, that TDP-43 assembles into amyloid filaments in ALS and type

SUBMITTER: Arseni D 

PROVIDER: S-EPMC10447236 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature