title: Prion-like mechanisms and potential therapeutic targets in neurodegenerative disorders.
abstract: Prion-like propagation of abnormal intracytoplasmic proteins, which are the defining features of major neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), has been proposed. A growing body of evidence strongly suggests that abnormal tau, α-synuclein and TDP-43 have prion-like properties, convert the corresponding normal proteins into abnormal forms, and are transmitted from cell to cell, spreading throughout the brain. This idea is extremely important not only for understanding the pathogenesis and progression of these diseases, but also for the development of molecular therapies. Since the distributions and spreading of the abnormal proteins are closely associated with disease symptoms and progression, gain-of-toxic-function of these proteins may affect the neurons and glial cells either directly or indirectly, or both. It is essential to regulate the aggregation of abnormal intracellular proteins and their cell-to-cell transmission in order to stop, or at least slow, the progression of these diseases.
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. Electronic address: hasegawa-ms@igakuken.or.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nonaka
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Masuda-Suzukake
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology / Q000628:therapy; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology / Q000628:therapy; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D019636:Neurodegenerative Diseases / Q000503:physiopathology* / Q000628:therapy; D010300:Parkinson Disease / Q000503:physiopathology / Q000628:therapy; D011328:Prions / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D011328:Prions; C000598624:TARDBP protein, human; D051844:alpha-Synuclein; D016875:tau Proteins
keywords: ALS; Alzheimer's disease; Parkinson's disease; TDP-43; Tau; α-synuclein