title: Prion-like properties of Tau protein: the importance of extracellular Tau as a therapeutic target.
abstract: Work over the past 4 years indicates that multiple proteins associated with neurodegenerative diseases, especially Tau and α-synuclein, can propagate aggregates between cells in a prion-like manner. This means that once an aggregate is formed it can escape the cell of origin, contact a connected cell, enter the cell, and induce further aggregation via templated conformational change. The prion model predicts a key role for extracellular protein aggregates in mediating progression of disease. This suggests new therapeutic approaches based on blocking neuronal uptake of protein aggregates and promoting their clearance. This will likely include therapeutic antibodies or small molecules, both of which can be developed and optimized in vitro prior to preclinical studies.
authors.affiliation: From the Department of Neurology, Washington University in St. Louis, St. Louis, Missouri 63110.
authors.forename: Brandon B
authors.initials: BB
authors.lastname: Holmes
authors.affiliation: From the Department of Neurology, Washington University in St. Louis, St. Louis, Missouri 63110 diamondm@neuro.wustl.edu.
authors.forename: Marc I
authors.initials: MI
authors.lastname: Diamond
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D055503:Protein Multimerization; D021381:Protein Transport; D024801:Tauopathies / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D014612:Vaccines / Q000276:immunology / Q000627:therapeutic use; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D019812:Heparan Sulfate Proteoglycans; D011328:Prions; D014612:Vaccines; D051844:alpha-Synuclein; D016875:tau Proteins
keywords: Aggregate Propagation; Alpha-Synuclein (a-Synuclein); Chemoprevention; Neurodegenerative Disease; Prion; Tau Protein (Tau); Therapy