The role of the ZEB1–neuroinflammation axis in CNS disorders

• Published in: Journal of neuroinflammation Vol. 19; no. 1; pp. 1 - 16
• Main Authors: Poonaki, Elham, Kahlert, Ulf Dietrich, Meuth, Sven G., Gorji, Ali
• Format: Journal Article
• Language: English
• Published: London BioMed Central 19.11.2022; BioMed Central Ltd; BMC
• Subjects: Alzheimer's disease; Angiogenesis; Apoptosis; Astrocytes; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Brain cancer; Brain tumors; Cell proliferation; Central nervous system diseases; Cerebrovascular diseases; Cytology; Diagnosis; Epithelial cells; Gene expression; Genetic aspects; Glioblastoma; Health aspects; Homeobox; Homeobox genes; Homeotic genes; Immunology; Inflammation; Invasiveness; Kinases; Mesenchyme; Metabolism; Metastasis; Microglia; MicroRNA; Multiple sclerosis; Mutation; Neural stem cells; Neuralgia; Neurobiology; Neurological disorders; Neurology; Neurosciences; Prostate; Proteins; Review; Risk factors; Stem cells; Therapeutic targets; Thymus gland; Transcription factors; Tumorigenesis; Tumors; Vascular diseases; Wound healing; Zinc finger proteins; Germany; Neural stem cells; MicroRNA; Metastasis; Glioblastoma; Microglia
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-022-02636-2

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.