Puranik Nidhi, Song Minseok
Department of Life Sciences, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Molecules. 2024 Dec 5;29(23):5744. doi: 10.3390/molecules29235744.
Gamma-glutamate is an important excitatory neurotransmitter in the central nervous system (CNS), which plays an important role in transmitting synapses, plasticity, and other brain activities. Nevertheless, alterations in the glutamatergic signaling pathway are now accepted as a central element in Alzheimer's disease (AD) pathophysiology. One of the most prevalent types of dementia in older adults is AD, a progressive neurodegenerative illness brought on by a persistent decline in cognitive function. Since AD has been shown to be multifactorial, a variety of pharmaceutical targets may be used to treat the condition. N-methyl-D-aspartic acid receptor (NMDAR) antagonists and acetylcholinesterase inhibitors (AChEIs) are two drug classes that the Food and Drug Administration has authorized for the treatment of AD. The AChEIs approved to treat AD are galantamine, donepezil, and rivastigmine. However, memantine is the only non-competitive NMDAR antagonist that has been authorized for the treatment of AD. This review aims to outline the involvement of glutamate (GLU) at the molecular level and the signaling pathways that are associated with AD to demonstrate the drug target therapeutic potential of glutamate and its receptor. We will also consider the opinion of the leading authorities working in this area, the drawback of the existing therapeutic strategies, and the direction for the further investigation.
γ-谷氨酸是中枢神经系统（CNS）中一种重要的兴奋性神经递质，在突触传递、可塑性及其他脑活动中发挥着重要作用。然而，谷氨酸能信号通路的改变如今被认为是阿尔茨海默病（AD）病理生理学的核心要素。AD是老年人中最常见的痴呆类型之一，是一种由认知功能持续衰退引发的进行性神经退行性疾病。由于已证明AD是多因素导致的，因此可采用多种药物靶点来治疗该病。N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂和乙酰胆碱酯酶抑制剂（AChEIs）是美国食品药品监督管理局已批准用于治疗AD的两类药物。被批准用于治疗AD的AChEIs有加兰他敏、多奈哌齐和卡巴拉汀。然而，美金刚是唯一已被批准用于治疗AD的非竞争性NMDAR拮抗剂。本综述旨在概述谷氨酸（GLU）在分子水平的参与情况以及与AD相关的信号通路，以证明谷氨酸及其受体作为药物靶点的治疗潜力。我们还将考虑该领域主要权威人士的观点、现有治疗策略的缺点以及进一步研究的方向。
