The HSF connection: Pleiotropic regulation and activities of Heat Shock Factors shape pathophysiological brain development

NEUROSCIENCE LETTERS

卷:725

Review

Duchateau, Agathe^1,2,3  de Thonel, Aurelie^1,2  El Fatimy, Rachid^1,2,4,5  Dubreuil, Veronique^1,2  Mezger, Valerie^1,2 

[1] Univ Paris, CNRS, Epigenet & Cell Fate, F-75013 Paris, France

[2] Dept Hosp Univ DHU PROTECT, Paris, France

[3] Univ Paris, ED BioSPC 562, F-75205 Paris 13, France

[4] Brigham & Womens Hosp, Dept Neurol, Ann Romney Ctr Neurol Dis, 60 Fenwood Rd,9006, Boston, MA 02115 USA

[5] Harvard Med Sch, 60 Fenwood Rd,9006, Boston, MA 02115 USA

关键词: Heat shock transcription factors;    HSFs;    Neurodevelopment;    Prenatal stress;    Transcription;    Vertebrates;   

DOI  :  10.1016/j.neulet.2020.134895

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free