Stress-Sensitive Protein Rac1 and Its Involvement in Neurodevelopmental Disorders

• 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
• Journal Title: NEURAL PLASTICITY
• Volume: Volume 2020
• Publisher: HINDAWI LTD | 2020-11-24, Pages 8894372-8894372
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1155/2020/8894372
• Subjects: Health Sciences, Epidemiology; Chemistry, Pharmaceutical
• Keywords: Science & Technology; Life Sciences & Biomedicine; Neurosciences; Neurosciences & Neurology; FRAGILE-X-SYNDROME; AUTISM SPECTRUM DISORDER; SMALL-MOLECULE INHIBITOR; SMALL GTPASE RAC1; NMDA RECEPTOR; RETT-SYNDROME; MENTAL-RETARDATION; DENDRITIC SPINES; COFILIN PHOSPHORYLATION; NEUROTROPHIC FACTOR

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.