为什么调节含 α6 的 GABAA 受体能减轻多种神经精神疾病的症状?

Werner Sieghart
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引用次数: 0

摘要

含α6的GABAA受体(α6GABAARs)在小脑颗粒细胞中强烈表达,它们在小脑颗粒细胞中介导所有执行行为的肌肉群的正确定时和精确协调,并保护大脑免受信息溢出的影响。最近的研究表明,对α6GABAARs具有高度选择性的正性调节剂(α6-调节剂)可以在相应的动物模型中减轻多种神经精神疾病的症状,其程度可媲美现有的临床疗法。本文将对这些令人难以置信的发现进行讨论和解释。迄今为止,α6-调节剂的有益作用及其无副作用仅在相关疾病的动物模型中得到证实。临床前研究已证明它们适合进一步的药物开发。未来的人体研究必须对其安全性和可能的副作用进行调查,并明确α6-调节剂在急性和慢性用药期间能在多大程度上减轻患者的各种疾病症状。由于α6-调节剂具有广泛的治疗潜力,因此可能成为治疗多种神经精神疾病的一种有价值的新选择。
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Why Can Modulation of α6-Containing GABAA Receptors Reduce the Symptoms of Multiple Neuropsychiatric Disorders?

α6-containing GABAA receptors (α6GABAARs) are strongly expressed in cerebellar granule cells, where they mediate a correctly timed and precise coordination of all muscle groups that execute behavior and protect the brain from information overflow. Recently, it was demonstrated that positive modulators with a high selectivity for α6GABAARs (α6-modulators) can reduce the symptoms of multiple neuropsychiatric disorders in respective animal models to an extent comparable with established clinical therapeutics. Here, these incredible findings are discussed and explained. So far, the beneficial actions of α6-modulators and their lack of side effects have only been demonstrated in animal models of the respective disorders. Preclinical studies have demonstrated their suitability for further drug development. Future human studies have to investigate their safety and possible side effects, and to clarify to which extent individual symptoms of the respective disorders can be reduced by α6-modulators in patients during acute and chronic dosing. Due to their broad therapeutic potential, α6-modulators might become a valuable new treatment option for multiple neuropsychiatric disorders.

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Why Can Modulation of α6-Containing GABAA Receptors Reduce the Symptoms of Multiple Neuropsychiatric Disorders?
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