title: Immunolocalization of Tom1 in relation to protein degradation systems in Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Neurology, Gunma University Graduate School of Medicine, Gunma, Japan. Electronic address: makiokakoki@yahoo.co.jp.
authors.forename: Kouki
authors.initials: K
authors.lastname: Makioka
authors.affiliation: Gunma University School of Health Sciences, Gunma, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Geriatrics Research Institute and Hospital, Gunma, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Takatama
authors.affiliation: Department of Neurology, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital & Institute of Gerontology, Itabashi-ku, Tokyo, Japan; Department of Neurology, Tokyo Metropolitan Geriastric Hospital & Institute of Gerontrogy, Itbashi-ku, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murayama
authors.affiliation: Geriatrics Research Institute and Hospital, Gunma, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Neurology, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016501:Neurites / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000473:pathology; D011506:Proteins / Q000378:metabolism*; D059748:Proteolysis; D014452:Ubiquitins / Q000378:metabolism; D024723:Ventricular Myosins / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D047908:Intracellular Signaling Peptides and Proteins; D052119:Lysosomal-Associated Membrane Protein 2; D011506:Proteins; C410602:TOLLIP protein, human; C120296:TOM1 protein, human; D014452:Ubiquitins; C018589:lysosomal proteins; D016875:tau Proteins; D024723:Ventricular Myosins
keywords: Alzheimer's disease; Autophagy; Dystrophic neurites; Myosin IV; Perisomatic granules; Tollip; Tom1 (target of Myb1); Ubiquitin