Immunolocalization of Tom1 in relation to protein degradation systems in Alzheimer's disease.
Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Its pathological hallmarks are senile plaques (SPs), which contain extracellular deposits of amyloid β (Aβ) protein fibrils and dystrophic neurites (DNs), and neurofibrillary tangles (NFTs) containing hyperphosphorylated tau. Impairment of protein-degradation systems, including the ubiquitin-proteasome and the autophagy-lysosome systems, has been proposed as one of the causes of the accumulation of these aberrant proteins in AD brains. Tom1 (target of Myb1) was originally identified by the induction of its expression by the v-Myb oncogene and is a part of two major protein-degradation systems. The present study was conducted by immunohistochemical and immunofluorescent stainings to show that Tom1 was localized in DNs, perisomatic granules (PSGs), and NFTs in AD brains. Moreover, in DNs, Tom1 colocalized with ubiquitin, lysosomal proteins, and Tom1-related proteins (Tollip and myosin VI), which act in both protein-degradation systems via Tom1. These results indicate that Tom1 plays important roles in protein-degradation systems in AD pathogenesis.
['Makioka|Kouki|K|', 'Yamazaki|Tsuneo|T|', 'Takatama|Masamitsu|M|', 'Ikeda|Masaki|M|', 'Murayama|Shigeo|S|', 'Okamoto|Koichi|K|', 'Ikeda|Yoshio|Y|']
D000368:Aged D000369:Aged, 80 and over D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D001921:Brain D005260:Female D006801:Humans D047908:Intracellular Signaling Peptides and Proteins D052119:Lysosomal-Associated Membrane Protein 2 D008297:Male D008875:Middle Aged D016501:Neurites D016874:Neurofibrillary Tangles D009474:Neurons D011506:Proteins D059748:Proteolysis D014452:Ubiquitins D024723:Ventricular Myosins D016875:tau Proteins
Alzheimer's disease Dystrophic neurites Tom1 (target of Myb1) Perisomatic granules Ubiquitin Tollip Autophagy Myosin IV