title: Synergy and antagonism of macroautophagy and chaperone-mediated autophagy in a cell model of pathological tau aggregation.
abstract: Tau aggregation characterizes a series of neurodegenerative diseases including AD and other tauopathies. The distribution of Tau deposits correlates with the loss of neurons in these neurodegenerative diseases, and Tau-induced toxicity depends on its ability to aggregate. We have used an inducible cell model to study the expression of Tau variants, the buildup of aggregates, and their removal by the autophagy-lysosomal system. Incomplete chaperone-mediated autophagy of Tau generates amyloidogenic fragments that promote aggregation. The Tau aggregates are removed from cells by macroautophagy. Thus the two autophagic pathways could become possible therapeutic targets.
authors.affiliation: Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Marta
authors.initials: M
authors.lastname: Martinez-Vicente
authors.forename: Ulrike
authors.initials: U
authors.lastname: Krüger
authors.forename: Susmita
authors.initials: S
authors.lastname: Kaushik
authors.forename: Esther
authors.initials: E
authors.lastname: Wong
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Mandelkow
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Cuervo
authors.forename: Eckhard
authors.initials: E
authors.lastname: Mandelkow
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002477:Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D018832:Molecular Chaperones; D016875:tau Proteins