| First Author | Lin LT | Year | 2021 |
| Journal | FASEB J | Volume | 35 |
| Issue | 5 | Pages | e21594 |
| PubMed ID | 33908654 | Mgi Jnum | J:308816 |
| Mgi Id | MGI:6741338 | Doi | 10.1096/fj.202002645R |
| Citation | Lin LT, et al. (2021) Hsp90 and its co-chaperone Sti1 control TDP-43 misfolding and toxicity. FASEB J 35(5):e21594 |
| abstractText | 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. |
