Huang Mengbing, Wang Ji, Liu Wei, Zhou Hongyan
Hubei Key Laboratory of Cognitive and Affective Disorders, Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China.
Front Neurosci. 2024 Jan 25;18:1349409. doi: 10.3389/fnins.2024.1349409. eCollection 2024.
The growth arrest and DNA damage inducible protein 45 (GADD45) family comprises stress-induced nuclear proteins that interact with DNA demethylases to facilitate DNA demethylation, thereby regulating diverse cellular processes including oxidative stress, DNA damage repair, apoptosis, proliferation, differentiation, inflammation, and neuroplasticity by modulating the expression patterns of specific genes. Widely expressed in the central nervous system, the GADD45 family plays a pivotal role in various neurological disorders, rendering it a potential therapeutic target for central nervous system diseases. This review presented a comprehensive overview of the expression patterns and potential mechanisms of action associated with each member of GADD45 family (GADD45α, GADD45β, and GADD45γ) in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders, while also explored strategies to harness these mechanisms for intervention and treatment. Future research should prioritize the development of effective modulators targeting the GADD45 family for clinical trials aimed at treating central nervous system diseases.
生长停滞和DNA损伤诱导蛋白45(GADD45)家族由应激诱导的核蛋白组成,这些蛋白与DNA去甲基化酶相互作用以促进DNA去甲基化,从而通过调节特定基因的表达模式来调控包括氧化应激、DNA损伤修复、细胞凋亡、增殖、分化、炎症和神经可塑性在内的多种细胞过程。GADD45家族在中枢神经系统中广泛表达,在各种神经系统疾病中起关键作用,使其成为中枢神经系统疾病的潜在治疗靶点。本综述全面概述了GADD45家族各成员(GADD45α、GADD45β和GADD45γ)在神经发育、神经退行性和神经精神疾病中的表达模式及潜在作用机制,同时还探讨了利用这些机制进行干预和治疗的策略。未来的研究应优先开发针对GADD45家族的有效调节剂,用于治疗中枢神经系统疾病的临床试验。