Dysfunction of RNA metabolism in TDP-43 proteinopathies: Elucidation of mechanism in stress granule formaion

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Stress granules are dense aggregations in the cytosol composed of RNAs and RNA binding proteins that appear when the cell is under stress. To elucidate the significance of stress granule formation in the disease process of neurodegenerative diseases, we examined immunoreactivity for stress granule marker proteins in tauopathies, synucleinopathies, TDP-43 proteinopathies and polyglutamine diseases. Cytoplasmic and nuclear inclusions proved to be immunopositive for stress granule marker proteins, leading to the hypothesis that stress granules play important roles for disease mechanisms in the development of neurodegenerative diseases. These inclusions were also immunopositive for some proteins associated with familial amyotrophic lateral sclerosis (fALS), one of TDP-43 proteinopathies. These results suggested that stress granules marker proteins and fALS-associated proteins may be therapeutic targets to prevent neurodegenerative diseases.