Inhibition of proteolysis enhances aluminum-induced perikaryal neurofilament accumulation but does not enhance tau accumulation

摘要: As observed for neuronsin situ, phosphorylated neurofilament (NF) epitopes are normally segregated within the axonal cytoskeleton of NB2a/d1 cells. However, accumulations NFs develop in perikarya following, exposure to aluminum salts and following inhibition proteolysis. In present study, we that cells exposed both protease inhibitor C1 (also known as “AllNal”) were more intensely labeled by monoclonal antibodies directed against nonphosphorylated than treated with either or alone. Since these crossreact tau, also immunostained under conditions phosphate-insensitive (5E2) (PHF-1) tau. Aluminum treatment, but not induced accumulation total tau isoforms judged an increase 5E2 immunoreactivity Neither separately combination, PHF-1 immunoreactivity. These findings suggest alterations SMI reflected increases NF epitopes. This was confirmed immunoblot analyses. proteolysis is apparently instrumental maintaining normal distribution patterns epitopes, implicate deficiencies proteolytic mechanisms development neurofibrillary pathology, underscore possibility a multiple etiology human neuropathological conditions.