Impaired NHEJ repair in amyotrophic lateral sclerosis is associated with TDP-43 mutations.

ABSTRACT:

Background

Pathological forms of TAR DNA-binding protein 43 (TDP-43) are present in motor neurons of almost all amyotrophic lateral sclerosis (ALS) patients, and mutations in TDP-43 are also present in ALS. Loss and gain of TDP-43 functions are implicated in pathogenesis, but the mechanisms are unclear. While the RNA functions of TDP-43 have been widely investigated, its DNA binding roles remain unclear. However, recent studies have implicated a role for TDP-43 in the DNA damage response.

Methods

We used NSC-34 motor neuron-like cells and primary cortical neurons expressing wildtype TDP-43 or TDP-43 ALS associated mutants (A315T, Q331K), in which DNA damage was induced by etoposide or H₂O₂ treatment. We investigated the consequences of depletion of TDP-

SUBMITTER: Konopka A 

PROVIDER: S-EPMC7488163 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature