Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, Mekelle, Ethiopia.
Biomed Res Int. 2018 May 14;2018:4160247. doi: 10.1155/2018/4160247. eCollection 2018.
Alzheimer's disease is a neurodegenerative disease characterized by deposition of extracellular amyloid-, intracellular neurofibrillary tangles, and loss of cortical neurons. However, the mechanism underlying neurodegeneration in Alzheimer's disease (AD) remains to be explored. Many of the researches on AD have been primarily focused on neuronal changes. Current research, however, broadens to give emphasis on the importance of nonneuronal cells, such as astrocytes. Astrocytes play fundamental roles in several cerebral functions and their dysfunctions promote neurodegeneration and, eventually, retraction of neuronal synapses, which leads to cognitive deficits found in AD. Astrocytes become reactive as a result of deposition of A, which in turn have detrimental consequences, including decreased glutamate uptake due to reduced expression of uptake transporters, altered energy metabolism, altered ion homeostasis (K and Ca), increased tonic inhibition, and increased release of cytokines and inflammatory mediators. In this review, recent insights on the involvement of, tonic inhibition, astrocytic glutamate transporters and aquaporin in the pathogenesis of Alzheimer's disease are provided. Compounds which increase expression of GLT1 have showed efficacy for AD in preclinical studies. Tonic inhibition mediated by GABA could also be a promising target and drugs that block the GABA synthesizing enzyme, MAO-B, have shown efficacy. However, there are contradictory evidences on the role of AQP4 in AD.
阿尔茨海默病是一种神经退行性疾病，其特征是细胞外淀粉样蛋白沉积、细胞内神经原纤维缠结和皮质神经元丧失。然而，阿尔茨海默病（AD）神经退行性变的机制仍有待探索。许多 AD 的研究主要集中在神经元变化上。然而，目前的研究范围扩大，强调非神经元细胞的重要性，如星形胶质细胞。星形胶质细胞在许多大脑功能中起着基本作用，其功能障碍会促进神经退行性变，最终导致神经元突触回缩，从而导致 AD 中发现的认知缺陷。由于 A 的沉积，星形胶质细胞变得活跃，这反过来又会产生有害的后果，包括由于摄取转运蛋白表达减少而导致的谷氨酸摄取减少、能量代谢改变、离子动态平衡改变（K 和 Ca）、持续抑制增加以及细胞因子和炎症介质的释放增加。在这篇综述中，提供了关于星形胶质细胞在阿尔茨海默病发病机制中涉及的持续抑制、星形胶质细胞谷氨酸转运体和水通道蛋白的最新见解。在临床前研究中，增加 GLT1 表达的化合物已显示出对 AD 的疗效。由 GABA 介导的持续抑制也可能是一个有前途的靶点，并且已经显示出抑制 GABA 合成酶 MAO-B 的药物有效。然而，AQP4 在 AD 中的作用存在矛盾的证据。
