JOURNAL ARTICLE
REVIEW

Pathogenic TARDBP mutations in amyotrophic lateral sclerosis and frontotemporal dementia: disease-associated pathways

Sami J Barmada, Steven Finkbeiner
Reviews in the Neurosciences 2010, 21 (4): 251-72
21086759
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are late-onset neurodegenerative disorders that are associated with mutations in the TARDBP gene. The product of this gene, TDP-43, has also been identified as the main component of the intracellular inclusions typical of most cases of ALS and FTD. Recent evidence suggests that TDP-43 is essential for proper development and involved in several fundamental cellular processes, including gene transcription, RNA processing, and the spatial regulation of mRNA translation. Pathogenic TARDBP mutations that impair TDP-43 function could therefore be related to neuronal degeneration in ALS and FTD. Conversely, cellular and animal studies have shown that pathogenic TARDBP mutations induce neuronal toxicity through mislocalization or elevated concentrations of TDP-43, consistent with a gain-of-function mechanism. In this review, we focus on the physiologic functions of TDP-43 within the central nervous system and discuss how these functions may be perturbed or pathologically altered by disease-associated mutations.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
21086759
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"