Volume 31, No 9, Sep 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 9, September 2021: 1024-1027

LETTERS TO THE EDITOR

Hsp70 chaperones TDP-43 in dynamic, liquid-like phase and prevents it from amyloid aggregation

Jinge Gu^1,2,† , Chen Wang^1,2,† , Rirong Hu^1,2,† , Yichen Li³ , Shengnan Zhang^1,2 , Yunpeng Sun^1,2 , Qiangqiang Wang¹ , Dan Li³ , Yanshan Fang^1,2,* , Cong Liu^1,2,*

¹Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China
²University of Chinese Academy of Sciences, Beijing, China
³Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China
^†These authors contributed equally: Jinge Gu, Chen Wang, Rirong Hu
Correspondence: Yanshan Fang(fangys@sioc.ac.cn)Cong Liu(liulab@sioc.ac.cn)

Dear Editor,

TAR DNA-binding protein 43 kDa (TDP-43) undergoes liquid–liquid phase separation (LLPS) and forms reversible, cytoprotective nuclear bodies (NBs) under stress.1 Abnormal liquid-to-solid phase transition condenses TDP-43 into irreversible pathological fibril, which is associated with neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD).2,3 However, the mechanisms by which cells maintain the highly aggregation-prone protein in the liquid-like phase and prevent TDP-43 NBs from aggregation under stressed conditions remain elusive. Molecular chaperones play a crucial role in maintaining protein homeostasis. Heat shock protein (Hsp) 70 can interact with TDP-434 and increase of Hsp70 suppresses TDP-43-mediated toxicity in fly models.5 Importantly, ALS patients with TDP-43 aggregates exhibit significantly decreased Hsp70 levels,6 suggesting that Hsp70 maintains TDP-43 proteostasis and that its dysregulation may be involved in pathological aggregation of TDP-43 RNA–protein granules in ALS and related diseases.

https://doi.org/10.1038/s41422-021-00526-5

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