TARDBP and proteostasis deficiencies: Regarding toxic protein aggregates, Meyerowitz et al. observed that chronic oxidative and nitrosative stress induced several features consistent with TDP-43 (the polypeptide product of the TARDBP gene) proteinopathies including loss of nuclear TDP-43, accumulation of diffuse TDP-43 in the cytosol, formation of a 35-kDa C-terminal fragment and accumulation of TDP-43 in RNA stress granules, some of which revealed ubiquitination [81].