Neuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USA.
Neuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USA.
Neuron. 2017 Dec 6;96(5):989-1001. doi: 10.1016/j.neuron.2017.10.001.
Targeted therapy for neuropsychiatric disorders requires selective modulation of dysfunctional neuronal pathways. Receptors relevant to CNS disorders typically have associated proteins discretely expressed in specific neuronal pathways; these accessory proteins provide a new dimension for drug discovery. Recent studies show that targeting a TARP auxiliary subunit of AMPA receptors selectively modulates neuronal excitability in specific forebrain pathways relevant to epilepsy. Other medicinally important ion channels, gated by glutamate, γ-aminobutyric acid (GABA), and acetylcholine, also have associated proteins, which may be druggable. This emerging pharmacology of receptor-associated proteins provides a new approach for improving drug efficacy while mitigating side effects.
针对神经精神疾病的靶向治疗需要选择性地调节功能失调的神经元通路。与 CNS 疾病相关的受体通常在特定的神经元通路上有离散表达的相关蛋白；这些辅助蛋白为药物发现提供了一个新的维度。最近的研究表明，靶向 AMPA 受体的 TARP 辅助亚基选择性地调节与癫痫相关的特定前脑通路中的神经元兴奋性。其他具有医学重要性的离子通道，由谷氨酸、γ-氨基丁酸（GABA）和乙酰胆碱门控，也有相关蛋白，这些蛋白可能是可成药的。这种新兴的受体相关蛋白药理学为提高药物疗效同时减轻副作用提供了一种新的方法。
