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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Hsp90 and its co-chaperone Sti1 control TDP-43 misfolding and toxicity

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Author(s):
Lin, Lilian Tsai-Wei [1] ; Razzaq, Abdul [2] ; Di Gregorio, Sonja E. [1] ; Hong, Soojie [1] ; Charles, Brendan [1] ; Lopes, Marilene H. [3, 4, 2] ; Beraldo, Flavio [2, 5] ; Prado, Vania F. [4, 2, 5] ; Prado, Marco A. M. [4, 2, 5] ; Duennwald, Martin L. [1, 4]
Total Authors: 10
Affiliation:
[1] Univ Western Ontario, Schulich Sch Med & Dent, Dept Pathol & Lab Med, London, ON - Canada
[2] Univ Western Ontario, Schulich Sch Med & Dent, Robarts Res Inst, London, ON - Canada
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo - Brazil
[4] Univ Western Ontario, Schulich Sch Med & Dent, Dept Anat & Cell Biol, MSB 414, 1151 Richmond St, London, ON N6A 5C1 - Canada
[5] Univ Western Ontario, Schulich Sch Med & Dent, Dept Physiol & Pharmacol, London, ON - Canada
Total Affiliations: 5
Document type: Journal article
Source: FASEB JOURNAL; v. 35, n. 5 MAY 2021.
Web of Science Citations: 0
Abstract

Protein misfolding is a central feature of most neurodegenerative diseases. Molecular chaperones can modulate the toxicity associated with protein misfolding, but it remains elusive which molecular chaperones and co-chaperones interact with specific misfolded proteins. TDP-43 misfolding and inclusion formation are a hallmark of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Using yeast and mammalian neuronal cells we find that Hsp90 and its co-chaperone Sti1 have the capacity to alter TDP-43 misfolding, inclusion formation, aggregation, and cellular toxicity. Our data also demonstrate that impaired Hsp90 function sensitizes cells to TDP-43 toxicity and that Sti1 specifically interacts with and strongly modulates TDP-43 toxicity in a dose-dependent manner. Our study thus uncovers a previously unrecognized tie between Hsp90, Sti1, TDP-43 misfolding, and cellular toxicity. (AU)

FAPESP's process: 19/00341-9 - Regulation of proteostasis in pluripotent stem cells by the co-chaperone STIP1
Grantee:Marilene Hohmuth Lopes
Support type: Regular Research Grants
FAPESP's process: 16/00440-9 - Impact of co-chaperone STIP1 expression in the pluripotency acquision induced by Oct4 in murine fibroblasts
Grantee:Marilene Hohmuth Lopes
Support type: Scholarships abroad - Research