The role of the ZEB1-neuroinflammation axis in CNS disorders.

Elham Poonaki, Ulf Dietrich Kahlert, Sven G Meuth, Ali Gorji

Journal: Journal of neuroinflammation 2022;19(1):275

PMID: 36402997

Abstract

Zinc finger E-box binding homeobox 1 (ZEB1) is a master modulator of the epithelial-mesenchymal transition (EMT), a process whereby epithelial cells undergo a series of molecular changes and express certain characteristics of mesenchymal cells. ZEB1, in association with other EMT transcription factors, promotes neuroinflammation through changes in the production of inflammatory mediators, the morphology and function of immune cells, and multiple signaling pathways that mediate the inflammatory response. The ZEB1-neuroinflammation axis plays a pivotal role in the pathogenesis of different CNS disorders, such as brain tumors, multiple sclerosis, cerebrovascular diseases, and neuropathic pain, by promoting tumor cell proliferation and invasiveness, formation of the hostile inflammatory micromilieu surrounding neuronal tissues, dysfunction of microglia and astrocytes, impairment of angiogenesis, and dysfunction of the blood-brain barrier. Future studies are needed to elucidate whether the ZEB1-neuroinflammation axis could serve as a diagnostic, prognostic, and/or therapeutic target for CNS disorders.

© 2022. The Author(s).

Address: Department of Neurology, Faculty of Medicine, Heinrich-Heine-University, Düsseldorf, Germany.; Epilepsy Research Center, Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Domagkstr. 11, 48149, Münster, Germany.; Molecular and Experimental Surgery, Faculty of Medicine, University Clinic for General-, Visceral-, Vascular- and Transplantation Surgery, Otto-Von-Guericke-University, Magdeburg, Germany.; Epilepsy Research Center, Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Domagkstr. 11, 48149, Münster, Germany. [email protected].; Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran. [email protected].; Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. [email protected].
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