Are stress granules involved in the pathogenesis of Amyotrophic Lateral Sclerosis?
Stress granules are cytoplasmic inclusions that repress translation of a subset of RNAs in times of cellular stress, and several proteins implicated in neurodegeneration (i.e. Ataxin-2 and SMN) interact with stress granules. Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules. ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis. ALS mutations in FUS NLS can impair FUS nuclear localization, induce cytoplasmic inclusions and stress granules, and potentially perturb RNA metabolism.