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Autophagic Punctum

Synergy and antagonism of macroautophagy and chaperone-mediated autophagy in a cell model of pathological tau aggregation

Yipeng Wang, Marta Martinez-Vicente, Ulrike Krüger, Susmita Kaushik, Esther Wong, Eva-Maria Mandelkow, Ana Maria Cuervo and Eckhard Mandelkow

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.

Punctum to: Wang Y, Martinez-Vicente M, Krüger U, Kaushik S, Wong E, Mandelkow EM, Cuervo AM, Mandelkow E. Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing. Hum Mol Genet 2009; 18:4153-70; PMID: 19654187; DOI: 10.1093/hmg/ddp367.

Authors

Yipeng Wang

Max-Planck-Unit for Structural Molecular Biology; Hamburg, Germany

Marta Martinez-Vicente

Departments of Developmental and Molecular Biology and of Anatomy and Structural Biology; Marion Bessin Liver Research Center; Albert Einstein College of Medicine; Bronx, NY USA

Ulrike Krüger

Max-Planck-Unit for Structural Molecular Biology; Hamburg, Germany

Susmita Kaushik

Departments of Developmental and Molecular Biology and of Anatomy and Structural Biology; Marion Bessin Liver Research Center; Albert Einstein College of Medicine; Bronx, NY USA

Esther Wong

Departments of Developmental and Molecular Biology and of Anatomy and Structural Biology; Marion Bessin Liver Research Center; Albert Einstein College of Medicine; Bronx, NY USA

Eva-Maria Mandelkow

Max-Planck-Unit for Structural Molecular Biology; Hamburg, Germany

Ana Maria Cuervo

Departments of Developmental and Molecular Biology and of Anatomy and Structural Biology; Marion Bessin Liver Research Center; Albert Einstein College of Medicine; Bronx, NY USA

Eckhard Mandelkow Corresponding author: mand@mpasmb.desy.de

Max-Planck-Unit for Structural Molecular Biology; Hamburg, Germany