ARTICLE | Targets & Mechanisms

Aggregation party in ALS

September 16, 2010 7:00 AM UTC

Aggregation and mislocalization of TDP-43 are at the heart of amyotrophic lateral sclerosis, but it is difficult to manipulate the proteindirectly because of its broad role in cellular survival. University of Pennsylvania researchers now have found evidence that TDP-43 interacts with ataxin 2, an intracellular protein linked to another neurodegenerative disease, spinocerebellar ataxia, and think that inhibiting ataxin 2 activitycould provide a handle for preventing the toxicity caused by mislocalized TDP-43.1

Mutations in TAR DNA binding protein 43 (TDP-43; TARDBP) lead to certain rare cases of hereditary amyotrophic lateral sclerosis (ALS), and in a majority of ALS patients the normally soluble protein mislocalizes into aggregates.2 But tinkering with TDP-43 levels can disrupt neurological development, complicating efforts to study the protein's function in mice...