Wellstone Center for FSHD; Department of Cell and Developmental Biology
Medical Subject Headings
Amyotrophic Lateral Sclerosis; Animals; Cytoplasmic Granules; DNA-Binding Proteins; Environmental Exposure; Humans; Nerve Tissue Proteins; Prions; Protein Structure, Tertiary; RNA-Binding Protein FUS; Stress, Physiological
Cell Biology | Developmental Biology | Molecular Biology | Molecular Genetics | Musculoskeletal Diseases | Nervous System Diseases
Amyotrophic lateral sclerosis (ALS) is a fatal human neurodegenerative disease affecting primarily motor neurons. Two RNA-binding proteins, TDP-43 and FUS, aggregate in the degenerating motor neurons of ALS patients, and mutations in the genes encoding these proteins cause some forms of ALS. TDP-43 and FUS and several related RNA-binding proteins harbor aggregation-promoting prion-like domains that allow them to rapidly self-associate. This property is critical for the formation and dynamics of cellular ribonucleoprotein granules, the crucibles of RNA metabolism and homeostasis. Recent work connecting TDP-43 and FUS to stress granules has suggested how this cellular pathway, which involves protein aggregation as part of its normal function, might be coopted during disease pathogenesis.
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Citation: Li YR, King OD, Shorter J, Gitler AD. Stress granules as crucibles of ALS pathogenesis. J Cell Biol. 2013 Apr 29;201(3):361-72. doi: 10.1083/jcb.201302044. Link to article on publisher's site
Li, Yun R.; King, Oliver D.; Shorter, James; and Gitler, Aaron D., "Stress granules as crucibles of ALS pathogenesis" (2013). Wellstone Center for FSHD Publications and Presentations. 6.