【摘 要】
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Dear Editor,rnTAR 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 pathologic
【机 构】
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Interdisciplinary Research Center on Biology and Chemistry,Shanghai Institute of Organic Chemistry,C
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Dear Editor,rnTAR 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 sig-nificantly decreased Hsp70 levels,6 suggesting that Hsp70 main-tains TDP-43 proteostasis and that its dysregulation may be involved in pathological aggregation of TDP-43 RNA-protein granules in ALS and related diseases.
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