阳离子-氯离子共转运蛋白 KCC2 和 NKCC1 作为神经和神经精神疾病的治疗靶点。
Cation-Chloride Cotransporters KCC2 and NKCC1 as Therapeutic Targets in Neurological and Neuropsychiatric Disorders.
机构信息
Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
Pharmacology and Therapeutics, School of Medicine, Galway Neuroscience Centre, University of Galway, H91 W5P7 Galway, Ireland.
出版信息
Molecules. 2023 Jan 31;28(3):1344. doi: 10.3390/molecules28031344.
Neurological diseases including Alzheimer's, Huntington's disease, Parkinson's disease, Down syndrome and epilepsy, and neuropsychiatric disorders such as schizophrenia, are conditions that affect not only individuals but societies on a global scale. Current therapies offer a means for small symptomatic relief, but recently there has been increasing demand for therapeutic alternatives. The γ-aminobutyric acid (GABA)ergic signaling system has been investigated for developing new therapies as it has been noted that any dysfunction or changes to this system can contribute to disease progression. Expression of the K-Cl-2 (KCC2) and N-K-C1-1 (NKCC1) cation-chloride cotransporters (CCCs) has recently been linked to the disruption of GABAergic activity by affecting the polarity of GABA receptor signaling. KCC2 and NKCC1 play a part in multiple neurological and neuropsychiatric disorders, making them a target of interest for potential therapies. This review explores current research suggesting the pathophysiological role and therapeutic importance of KCC2 and NKCC1 in neuropsychiatric and neurological disorders.
神经退行性疾病包括阿尔茨海默病、亨廷顿病、帕金森病、唐氏综合征和癫痫，以及神经精神疾病如精神分裂症，这些疾病不仅影响个人，而且在全球范围内影响社会。目前的治疗方法提供了一种缓解症状的手段，但最近对治疗替代品的需求不断增加。γ-氨基丁酸（GABA）能信号系统一直被研究用于开发新的治疗方法，因为人们注意到，该系统的任何功能障碍或变化都可能导致疾病进展。最近，K-Cl-2（KCC2）和 N-K-C1-1（NKCC1）阳离子-氯离子共转运蛋白（CCCs）的表达与 GABA 能活性的破坏有关，通过影响 GABA 受体信号的极性。KCC2 和 NKCC1 在多种神经和神经精神疾病中发挥作用，使它们成为潜在治疗方法的关注目标。本综述探讨了目前的研究，这些研究表明 KCC2 和 NKCC1 在神经精神和神经退行性疾病中的病理生理作用和治疗重要性。
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