BIBTEX

@article{fe747ded456e410ea2f1556a6cc5b1a8, title = 'Truncated tau interferes with the autophagy and endolysosomal pathway and results in lipid accumulation', abstract = 'The autophagy-lysosomal pathway plays a critical role in the clearance of tau protein aggregates that deposit in the brain in tauopathies, and defects in this system are associated with disease pathogenesis. Here, we report that expression of Tau35, a tauopathy-associated carboxy-terminal fragment of tau, leads to lipid accumulation in cell lines and primary cortical neurons. Our findings suggest that this is likely due to a deleterious block of autophagic clearance and lysosomal degradative capacity by Tau35. Notably, upon induction of autophagy by Torin 1, Tau35 inhibited nuclear translocation of transcription factor EB (TFEB), a key regulator of lysosomal biogenesis. Both cell lines and primary cortical neurons expressing Tau35 also exhibited changes in endosomal protein expression. These findings implicate autophagic and endolysosomal dysfunction as key pathological mechanisms through which disease-associated tau fragments could lead to the development and progression of tauopathy.', keywords = 'Autophagy, tau Proteins/metabolism, Lysosomes/metabolism, Humans, Neurons/metabolism, Animals, Endosomes/metabolism, Lipid Metabolism, Tauopathies/metabolism, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism, Mice', author = 'Pollack, {Saskia J} and Dina Dakkak and Tong Guo and George Chennell and Patricia Gomez-Suaga and Wendy Noble and Maria Jimenez-Sanchez and Hanger, {Diane P}', note = 'Publisher Copyright: {\textcopyright} The Author(s) 2024.', year = '2024', month = jul, day = '15', doi = '10.1007/s00018-024-05337-6', language = 'English', volume = '81', pages = '304', journal = 'Cellular and molecular life sciences : CMLS', issn = '1420-682X', publisher = 'Birkhauser Verlag Basel', number = '1', }