TDP-43 Proteinopathy and ALS: Insights into Disease Mechanisms and Therapeutic Targets.

ABSTRACT: Therapeutic options for patients with amyotrophic lateral sclerosis (ALS) are currently limited. However, recent studies show that almost all cases of ALS, as well as tau-negative frontotemporal dementia (FTD), share a common neuropathology characterized by the deposition of TAR-DNA binding protein (TDP)-43-positive protein inclusions, offering an attractive target for the design and testing of novel therapeutics. Here we demonstrate how diverse environmental stressors linked to stress granule formation, as well as mutations in genes encoding RNA processing proteins and protein degradation adaptors, initiate ALS pathogenesis via TDP-43. We review the progressive development of TDP-43 proteinopathy from cytoplasmic mislocalization and misfolding through to macroaggregation and the addition

SUBMITTER: Scotter EL 

PROVIDER: S-EPMC4404432 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature