Current Enlightenment About Etiology and Pharmacological Treatment of Autism Spectrum Disorder.
Current Enlightenment About Etiology and Pharmacological Treatment of Autism Spectrum Disorder.
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DOI：
10.3389/fnins.2018.00304
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发表时间：
2018
影响因子：
4.3
通讯作者：
Sadek B
中科院分区：
文献类型：
--
作者：
Eissa N;Al-Houqani M;Sadeq A;Ojha SK;Sasse A;Sadek B
自闭症谱系障碍(ASD)是一种复杂的神经发育性大脑疾病，以两种核心行为症状为特征，即社交交流障碍和限制/重复行为。ASD的分子机制还不是很清楚。最近的遗传和非遗传动物模型在理解ASD的病理生理学方面做出了重大贡献，因为它们在小鼠和大鼠中建立了自闭症样行为。在遗传因素中，包括重复或缺失在内的多个染色体突变可能是ASD的可能致病因素。此外，生化基础表明，多巴胺(DA)、5-羟色胺(5-HT)、γ-氨基丁酸(GABA)、乙酰胆碱(ACh)、谷氨酸(Glu)和组胺(HA)等脑神经递质参与ASD的发生发展。尽管认识令人信服，但经美国食品和药物管理局(FDA)批准，利培酮和阿立哌唑是临床上仅有的两种可用于改善ASD行为症状的药物。到目前为止，据我们所知，还没有其他药物被批准用于临床专门治疗ASD症状。然而，在临床前和临床药物开发的不同阶段，许多新的候选药物和一类化合物正在用于ASD。本文综述了多种致病因素的多样性以及与ASD相关的神经递质的产生、释放和功能的变化，重点介绍了目前用于治疗ASD相关神经精神症状的药物。该综述还重点介绍了药物的临床开发，重点介绍了旨在改善ASD核心症状的药物的药理靶点。
Autistic Spectrum Disorder (ASD) is a complex neurodevelopmental brain disorder characterized by two core behavioral symptoms, namely impairments in social communication and restricted/repetitive behavior. The molecular mechanisms underlying ASD are not well understood. Recent genetic as well as non-genetic animal models contributed significantly in understanding the pathophysiology of ASD, as they establish autism-like behavior in mice and rats. Among the genetic causes, several chromosomal mutations including duplications or deletions could be possible causative factors of ASD. In addition, the biochemical basis suggests that several brain neurotransmitters, e.g., dopamine (DA), serotonin (5-HT), gamma-amino butyric acid (GABA), acetylcholine (ACh), glutamate (Glu) and histamine (HA) participate in the onset and progression of ASD. Despite of convincible understanding, risperidone and aripiprazole are the only two drugs available clinically for improving behavioral symptoms of ASD following approval by Food and Drug Administration (FDA). Till date, up to our knowledge there is no other drug approved for clinical usage specifically for ASD symptoms. However, many novel drug candidates and classes of compounds are underway for ASD at different phases of preclinical and clinical drug development. In this review, the diversity of numerous aetiological factors and the alterations in variety of neurotransmitter generation, release and function linked to ASD are discussed with focus on drugs currently used to manage neuropsychiatric symptoms related to ASD. The review also highlights the clinical development of drugs with emphasis on their pharmacological targets aiming at improving core symptoms in ASD.
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影响因子：
3.7
作者：
Baronio D;Castro K;Gonchoroski T;de Melo GM;Nunes GD;Bambini-Junior V;Gottfried C;Riesgo R
通讯作者：
Riesgo R
影响因子：
4.7
作者：
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通讯作者：
Laxmi, T. Rao
影响因子：
5.6
作者：
Alachkar A;Łażewska D;Kieć-Kononowicz K;Sadek B
通讯作者：
Sadek B
影响因子：
3.3
作者：
Arnold, HM;Burk, JA;Bruno, JP
通讯作者：
Bruno, JP
影响因子：
56.9
作者：
Bailey, JA;Gu, ZP;Eichler, EE
通讯作者：
Eichler, EE