Duchateau Agathe, de Thonel Aurélie, El Fatimy Rachid, Dubreuil Véronique, Mezger Valérie
Université de Paris, Epigenetics and Cell Fate, CNRS, F-75013, Paris, France; Département Hospitalo-Universitaire DHU PROTECT, Paris, France; ED 562 BioSPC, Université de Paris, F-75205, Paris Cedex 13, France.
Université de Paris, Epigenetics and Cell Fate, CNRS, F-75013, Paris, France; Département Hospitalo-Universitaire DHU PROTECT, Paris, France.
Neurosci Lett. 2020 Apr 23;725:134895. doi: 10.1016/j.neulet.2020.134895. Epub 2020 Mar 5.
The Heat Shock Factors (HSFs) have been historically identified as a family of transcription factors that are activated and work in a stress-responsive manner, after exposure to a large variety of stimuli. However, they are also critical in normal conditions, in a life long manner, in a number of physiological processes that encompass gametogenesis, embryonic development and the integrity of adult organs and organisms. The importance of such roles is emphasized by the devastating impact of their deregulation on health, ranging from reproductive failure, neurodevelopmental disorders, cancer, and aging pathologies, including neurodegenerative disorders. Here, we provide an overview of the delicate choreography of the regulation of HSFs during neurodevelopment, at prenatal and postnatal stages. The regulation of HSFs acts at multiple layers and steps, and comprises the control of (i) HSF mRNA and protein levels, (ii) HSF activity in terms of DNA-binding and transcription, (iii) HSF homo- and hetero-oligomerization capacities, and (iv) HSF combinatory set of post-translational modifications. We also describe how these regulatory mechanisms operate in the normal developing brain and how their perturbation impact neurodevelopment under prenatal or perinatal stress conditions. In addition, we put into perspective the possible role of HSFs in the evolution of the vertebrate brains and the importance of the HSF pathway in a large variety of neurodevelopmental disorders.
热休克因子（HSFs）在历史上被确定为一类转录因子，在受到多种刺激后被激活并以应激反应方式发挥作用。然而，它们在正常情况下也至关重要，在包括配子发生、胚胎发育以及成年器官和生物体完整性在内的许多生理过程中，以一种贯穿一生的方式发挥作用。它们失调对健康造成的毁灭性影响，从生殖失败、神经发育障碍、癌症到衰老病理（包括神经退行性疾病），都凸显了这些作用的重要性。在这里，我们概述了热休克因子在神经发育的产前和产后阶段的精细调控过程。热休克因子的调控作用于多个层面和步骤，包括对以下方面的控制：（i）热休克因子mRNA和蛋白质水平；（ii）热休克因子在DNA结合和转录方面的活性；（iii）热休克因子的同源和异源寡聚化能力；以及（iv）热休克因子翻译后修饰的组合集。我们还描述了这些调控机制在正常发育大脑中的运作方式，以及它们在产前或围产期应激条件下的扰动如何影响神经发育。此外，我们探讨了热休克因子在脊椎动物大脑进化中的可能作用，以及热休克因子途径在多种神经发育障碍中的重要性。
