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.
Rights and Permissions
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. 6.