Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Korea.
Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology, Seoul 02792, Korea.
Int J Mol Sci. 2022 Jun 10;23(12):6515. doi: 10.3390/ijms23126515.
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by repetitive and stereotyped behaviors as well as difficulties with social interaction and communication. According to reports for prevalence rates of ASD, approximately 1~2% of children worldwide have been diagnosed with ASD. Although there are a couple of FDA (Food and Drug Administration)-approved drugs for ASD treatment such as aripiprazole and risperidone, they are efficient for alleviating aggression, hyperactivity, and self-injury but not the core symptoms. Serotonin (5-hydroxytryptamine, 5-HT) as a neurotransmitter plays a crucial role in the early neurodevelopmental stage. In particular, 5-HT has been known to regulate a variety of neurobiological processes including neurite outgrowth, dendritic spine morphology, shaping neuronal circuits, synaptic transmission, and synaptic plasticity. Given the roles of serotonergic systems, the 5-HT receptors (5-HTRs) become emerging as potential therapeutic targets in the ASD. In this review, we will focus on the recent development of small molecule modulators of 5-HTRs as therapeutic targets for the ASD treatment.
自闭症谱系障碍（ASD）是一组神经发育障碍，其特征是重复和刻板的行为以及社交互动和沟通困难。根据 ASD 患病率的报告，全世界大约有 1%至 2%的儿童被诊断患有 ASD。尽管有几种经美国食品和药物管理局（FDA）批准的 ASD 治疗药物，如阿立哌唑和利培酮，但它们对缓解攻击性行为、多动和自残行为有效，但对核心症状无效。血清素（5-羟色胺，5-HT）作为一种神经递质，在早期神经发育阶段起着至关重要的作用。特别是，5-HT 已被证明可以调节多种神经生物学过程，包括神经突生长、树突棘形态、塑造神经元回路、突触传递和突触可塑性。鉴于血清素能系统的作用，5-羟色胺受体（5-HTRs）成为治疗 ASD 的潜在治疗靶点。在这篇综述中，我们将重点介绍 5-HTR 小分子调节剂作为治疗 ASD 的治疗靶点的最新进展。
