New Therapeutic Avenue for ALS: Avoiding a Fatal Encounter of TDP-43 at the Mitochondria

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common fatal neuromuscular disease in adults, and very limited options for clinical improvement are currently available.1 The etiology of ALS is complex and heterogeneous, with multiple genetic associations reported so far.2 Among these, the gene coding for TAR DNA-binding protein 43 (TDP-43) RNA/DNA binding protein was identified as the principal component of ubiquitinated cytoplasmic inclusions, which are one of the main pathological hallmarks observed in most familial and sporadic cases of ALS as well as in frontotemporal dementia with ubiquitin inclusions (FTD-U).