Stress-Sensitive Protein Rac1 and Its Involvement in Neurodevelopmental Disorders

• Type of Material: Article
• Authors: Xiaohui Wang, Capital Medical University; Dongbin Liu, Capital Medical University; Fangzhen Wei, Peking Univ Hosp; Yue Li, Guangwai Community Health Service Center of Xicheng District; Xuefang Wang, Guangwai Community Health Service Center of Xicheng District; Linje Li, Emory University; Guan Wang, Tsinghua University; Shuli Zhang, Chinese Academy of Sciences; Lei Zhang, Staidson (Beijing) Biopharmaceuticals Co., Ltd
• Language: English
• Date: 2020-11-24
• Publisher: HINDAWI LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Xiaohui Wang et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1155/2020/8894372
• Title of Journal or Parent Work: NEURAL PLASTICITY
• Volume: 2020
• Start Page: 8894372
• End Page: 8894372
• Grant/Funding Information: The work was supported by the grants of the National Science Foundation of China (Nos. 31527802 and 31871033) (S. Z.), the Beijing Natural Science Foundation (7182063), the Beijing Health System High-Level Health Technical Personnel (2014-3-058), and the Fund for Incubating Program of Capital Medical University (No. PYZ2018058) (X. H. W.).
• Keywords: DENDRITIC SPINES; COFILIN PHOSPHORYLATION; Science & Technology; SMALL GTPASE RAC1; AUTISM SPECTRUM DISORDER; FRAGILE-X-SYNDROME; Neurosciences; NEUROTROPHIC FACTOR; Life Sciences & Biomedicine; NMDA RECEPTOR; RETT-SYNDROME; Neurosciences & Neurology; SMALL-MOLECULE INHIBITOR; MENTAL-RETARDATION
• Research Categories: Health Sciences, Epidemiology; Chemistry, Pharmaceutical

Abstract

Ras-related C3 botulinum toxin substrate 1 (Rac1) is a small GTPase that is well known for its sensitivity to the environmental stress of a cell or an organism. It senses the external signals which are transmitted from membrane-bound receptors and induces downstream signaling cascades to exert its physiological functions. Rac1 is an important regulator of a variety of cellular processes, such as cytoskeletal organization, generation of oxidative products, and gene expression. In particular, Rac1 has a significant influence on certain brain functions like neuronal migration, synaptic plasticity, and memory formation via regulation of actin dynamics in neurons. Abnormal Rac1 expression and activity have been observed in multiple neurological diseases. Here, we review recent findings to delineate the role of Rac1 signaling in neurodevelopmental disorders associated with abnormal spine morphology, synaptogenesis, and synaptic plasticity. Moreover, certain novel inhibitors of Rac1 and related pathways are discussed as potential avenues toward future treatment for these diseases.