title: TDP-43 Prions.
abstract: The most common neurodegenerative diseases, such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, are all protein-misfolding diseases and are characterized by the presence of disease-specific protein aggregates in affected neuronal cells. Recent studies have shown that, like tau and α-synuclein, TAR-DNA binding protein of 43 kDa (TDP-43) can form aggregates in vitro in a seed-dependent, self-templating, prion-like manner. Insoluble TDP-43 prepared from the brains of patients has been classified into several strains, which can be transferred from cell to cell in vitro, suggesting the involvement of mechanisms reminiscent of those by which prions spread through the nervous system. The idea that aberrant TDP-43 aggregates propagate in a prion-like manner between cells presents the possibility of novel therapeutic strategies to block spreading of these aggregates throughout the brain.
authors.affiliation: Dementia Research Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan 156-8506.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nonaka
authors.affiliation: Dementia Research Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan 156-8506.
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry*; D004195:Disease Models, Animal; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology*; D009474:Neurons / Q000378:metabolism; D000072002:Prion Proteins / Q000737:chemistry*; D066263:Protein Aggregation, Pathological / Q000235:genetics / Q000473:pathology*; D057165:Proteostasis Deficiencies / Q000235:genetics / Q000473:pathology*
chemical_list: D004268:DNA-Binding Proteins; D000072002:Prion Proteins; C000598624:TARDBP protein, human