Centre for Brain Research, Faculty of Medical and Health Sciences, Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand.
J Neurochem. 2018 Sep;146(6):649-669. doi: 10.1111/jnc.14345. Epub 2018 Aug 1.
Glutamatergic and cholinergic dysfunction are well-attested features of Alzheimer's disease (AD), progressing with other pathological indices of the disorder and exacerbating neuronal and network dysfunction. However, relatively little attention has been paid to the inhibitory component of the excitatory/inhibitory (E/I) network, particularly dysfunction in the gamma-aminobutyric acid (GABA) signaling system. There is growing evidence in support of GABAergic remodeling in the AD brain, potentially beginning in early stages of disease pathogenesis, and this could thus be a valid molecular target for drug development and pharmacological therapies. Several GABAergic drugs have been tested for efficacy in attenuating or reversing various features and symptoms of AD, and this could represent a novel path by which we might address the growing need for more effective and benign therapies.
谷氨酸能和胆碱能功能障碍是阿尔茨海默病（AD）的明显特征，随着该疾病其他病理指标的进展而恶化，并加重神经元和网络功能障碍。然而，人们相对较少关注兴奋性/抑制性（E/I）网络的抑制成分，特别是γ-氨基丁酸（GABA）信号系统的功能障碍。越来越多的证据支持 AD 大脑中的 GABA 能重塑，这种重塑可能在疾病发病的早期阶段就开始了，因此这可能是药物开发和药理治疗的一个有效分子靶点。已经有几种 GABA 能药物被测试用于减轻或逆转 AD 的各种特征和症状的疗效，这可能代表了一种新的途径，我们可以通过这种途径来满足对更有效和更良性治疗方法的日益增长的需求。
