Synergy and antagonism of macroautophagy and chaperone-mediated autophagy in a cell model of pathological tau aggregation.
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.
Wang
Yipeng
Y
Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.
Martinez-Vicente
Marta
M
Krüger
Ulrike
U
Kaushik
Susmita
S
Wong
Esther
E
Mandelkow
Eva-Maria
EM
Cuervo
Ana Maria
AM
Mandelkow
Eckhard
E
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*
D018832:Molecular Chaperones; D016875:tau Proteins