Neurosteroids as regulators of neuroinflammation

• Published in: Frontiers in neuroendocrinology 2019-10, Vol.55, p.100788-100788, Article 100788
• Main Authors: Yilmaz, Canelif, Karali, Kanelina, Fodelianaki, Georgia, Gravanis, Achille, Chavakis, Triantafyllos, Charalampopoulos, Ioannis, Alexaki, Vasileia Ismini
• Format: Article
• Language: English
• Subjects: 17β-estradiol; Allopregnanolone; Alzheimer Disease - immunology; Alzheimer Disease - metabolism; Alzheimer’s disease; Animals; Astrocytes; Brain Injuries, Traumatic - immunology; Brain Injuries, Traumatic - metabolism; Dehydroepiandrosterone (DHEA); Estrogens; Female; Humans; Inflammation - immunology; Inflammation - metabolism; Male; Microglia; Multiple sclerosis; Multiple Sclerosis - immunology; Multiple Sclerosis - metabolism; Neuroinflammation; Neurosteroids; Neurosteroids - metabolism; Parkinson Disease - immunology; Parkinson Disease - metabolism; Parkinson’s disease; Progesterone; Progestogens; Traumatic brain injury
• ISSN: 0091-3022; 1095-6808
• DOI: 10.1016/j.yfrne.2019.100788

•Neuroinflammation is a hallmark of neurodegenerative diseases.•The central nervous system synthesizes and metabolizes steroids.•Neurosteroids can regulate inflammatory responses of microglia and astrocytes.•Synthetic analogs of neurosteroids could be candidates for the management of neuroinflammation. Neuroinflammation is a physiological protective response in the context of infection and injury. However, neuroinflammation, especially if chronic, may also drive neurodegeneration. Neurodegenerative diseases, such as multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s disease (PD) and traumatic brain injury (TBI), display inflammatory activation of microglia and astrocytes. Intriguingly, the central nervous system (CNS) is a highly steroidogenic environment synthesizing steroids de novo, as well as metabolizing steroids deriving from the circulation. Neurosteroid synthesis can be substantially affected by neuroinflammation, while, in turn, several steroids, such as 17β-estradiol, dehydroepiandrosterone (DHEA) and allopregnanolone, can regulate neuroinflammatory responses. Here, we review the role of neurosteroids in neuroinflammation in the context of MS, AD, PD and TBI and describe underlying molecular mechanisms. Moreover, we introduce the concept that synthetic neurosteroid analogues could be potentially utilized for the treatment of neurodegenerative diseases in the future.