阿尔茨海默病中的谷氨酸代谢

Glutamate metabolism in Alzheimer’s disease

阿尔茨海默病(AD)是人类最常见的神经退行性疾病,主要以进行性认知和记忆障碍为临床表现,其特征性病理改变为β-淀粉样肽(Aβ)在细胞外沉积形成的老年斑、细胞内神经纤维缠结(NFTs)出现、胆碱能神经元缺失、广泛的神经元丢失以及胶质细胞增生。AD的病因机制研究火热,但至今为止仍未被完全阐明。谷氨酸是哺乳动物大脑中最丰富的兴奋性神经递质,谷氨酸信号的神经传递在学习和记忆中起着至关重要的作用。谷氨酸稳态失衡被认为参与了AD神经病理特征的发展和认知功能下降。因此,了解谷氨酸的理化性质,谷氨酸在神经系统中的转运和代谢过程以及谷氨酸稳态与AD之间的疾病相关生物学可能会为AD的发病机制和治疗提供新的见解。

Alzheimer’s disease(AD)is the most common neurodegenerative disease in humans,with progressive cognitive and memory impairment as the main clinical manifestation.The characteristic pathological changes of AD are senile plaques formed by extracellular deposition ofβ-amyloid(Aβ)peptide,intracellular nerve fiber tangles(NFTs),loss of cholinergic neurons,and gliosis.The etiological mechanism of AD has been intensively studied but has not been clearly elucidated so far.Glutamate is the most abundant excitatory neurotransmitter in the mammalian brain,and neurotransmission of glutamate signals plays a crucial role in learning and memory.Imbalance of glutamate homeostasis has been thought to be involved in the development of neuropathological features and cognitive decline in AD.Therefore,nuderstanding the physicochemical properties of glutamate,the transport and metabolic processes of glutamate in the nervous system,and the disease-related biology between glutamate homeostasis and AD is likely to provide novel insights into the pathogenesis and treatment of AD.