HSF1A is an activator of Heat Shock Transcription Factor 1 (HSF1) [1]. HSF1A inhibits the activity of the molecular chaperone TRiC/CCT, thereby activating HSF1 and enhancing cellular resistance to protein misfolding and stress [2-3]. HSF1A is primarily used to treat neurodegenerative diseases [4].
In CD150+CD48-LSK hematopoietic stem cells (HSCs), HSF1A (8μM; 10d) enhances the serial reconstitutive activity of HSCs cultured in vitro [5]. In chinese hamster ovary cells, HSF1A (200µM; 1h) protects cells from pertussis toxin-induced cytotoxicity [6].
In wistar kyoto rats, HSF1A (100mg/kg; ip; 4 weeks) ameliorates doxorubicin-induced heart failure in vivo [7]. In ovalbumininduced allergic asthma mice model, HSF1A (1.3g/kg; ig; 5 weeks) treatment not only reduces inflammation and oxidative stress but also significantly attenuates airway fibrosis [8].
References:
[1]. Neef D W, Jaeger A M, Gomez-Pastor R, et al. A direct regulatory interaction between chaperonin TRiC and stress-responsive transcription factor HSF1[J]. Cell reports, 2014, 9(3): 955-966.
[2]. Neef D W, Turski M L, Thiele D J. Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease[J]. PLoS biology, 2010, 8(1): e1000291.
[3]. Steinemann M, Schlosser A, Jank T, et al. The chaperonin TRiC/CCT is essential for the action of bacterial glycosylating protein toxins like Clostridium difficile toxins A and B[J]. Proceedings of the National Academy of Sciences, 2018, 115(38): 9580-9585.
[4]. Liu A Y, Minetti C A, Remeta D P, et al. HSF1, aging, and neurodegeneration[J]. Cell Biology and Translational Medicine, Volume 18: Tissue Differentiation, Repair in Health and Disease, 2022: 23-49.
[5]. Kruta M, Sunshine M J, Chua B A, et al. Hsf1 promotes hematopoietic stem cell fitness and proteostasis in response to ex vivo culture stress and aging[J]. Cell stem cell, 2021, 28(11): 1950-1965. e6.
[6]. Jia J, Zoeschg M, Barth H, et al. The chaperonin TRiC/CCT inhibitor HSF1A protects cells from intoxication with pertussis toxin[J]. Toxins, 2024, 16(1): 36.
[7]. Huang C Y, Kuo W W, Lo J F, et al. Doxorubicin attenuates CHIP-guarded HSF1 nuclear translocation and protein stability to trigger IGF-IIR-dependent cardiomyocyte death[J]. Cell death & disease, 2016, 7(11): e2455-e2455.
[8]. Liu X, Zhang Y, Wu H, et al. HSF1 in macrophages suppressed the progression of asthma via modulating SIRPα/SHP2—Dectin-1/SYK mediated ROS and inflammatory responses[J]. Scientific Reports, 2025, 15(1): 29741.
HSF1A是热休克转录因子1（HSF1）的激活剂 [1]。HSF1A抑制分子伴侣TRiC/CCT的活性，从而激活HSF1，增强细胞对蛋白质错误折叠和应激的抵抗力 [2-3]。HSF1A主要用于治疗神经退行性疾病 [4]。
在CD150+CD48-LSK造血干细胞（HSC）中，HSF1A（8μM；10d）可增强体外培养的HSC的连续重建活性 [5]。在中国仓鼠卵巢细胞中，HSF1A（200μM；1h）可保护细胞免受百日咳毒素诱导的细胞毒性 [6]。
在wistar kyoto大鼠中，HSF1A（100 mg/kg；ip；4周）可改善体内阿霉素诱导的心力衰竭 [7]。在卵清蛋白诱导的过敏性哮喘小鼠模型中，HSF1A（1.3g/kg；ig；5周）治疗不仅可以减轻炎症和氧化应激，而且还可以显著减轻气道纤维化 [8]。