Lin Ping, Yang Jie, Wu Shumin, Ye Tong, Zhuang Wenting, Wang Wei, Tan Tao
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States.
Front Psychiatry. 2023 Jul 28;14:1215110. doi: 10.3389/fpsyt.2023.1215110. eCollection 2023.
Cul3 encodes Cullin-3, a core component of the ubiquitin E3 ligase that is involved in protein ubiquitination. Recent studies have identified Cul3 as a high-confidence risk gene in neurodevelopmental disorders (NDDs), especially autism spectrum disorder (ASD). Different strategies have been used to generate animal models with Cul3 deficiency in the central nervous system, including whole-brain knockout (KO), cell-type specific conditional KO (cKO), and brain region-specific knockdown. In this review, we revisited the basic properties of CUL3 and its function under physiological and pathological conditions. Recent clinical studies including case reports and large cohort sequencing studies related to CUl3 in NDDs have been summarized. Moreover, we characterized the behavioral, electrophysiological, and molecular changes in newly developed Cul3 deficiency models. This would guide further studies related to Cul3 in CNS and provide potential therapeutic targets for Cul3-deficiency-induced NDDs, including ASD.
Cul3编码Cullin-3，它是泛素E3连接酶的核心成分，参与蛋白质泛素化过程。最近的研究已将Cul3确定为神经发育障碍（NDDs），尤其是自闭症谱系障碍（ASD）中的一个高可信度风险基因。人们采用了不同策略来构建中枢神经系统中Cul3缺陷的动物模型，包括全脑敲除（KO）、细胞类型特异性条件性敲除（cKO）和脑区特异性敲低。在本综述中，我们重新审视了CUL3的基本特性及其在生理和病理条件下的功能。总结了近期包括病例报告和与NDDs中Cul3相关的大型队列测序研究在内的临床研究。此外，我们还描述了新构建的Cul3缺陷模型中的行为、电生理和分子变化。这将为中枢神经系统中与Cul3相关的进一步研究提供指导，并为包括ASD在内的Cul3缺陷所致NDDs提供潜在的治疗靶点。
