{"title":"AD大脑中d -丝氨酸水平动态变化的复杂过程。","authors":"Xiance Ni, Hisashi Mori","doi":"10.2174/1567205019666220328123048","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular β-amyloid (Aβ) plaques and cognitive impairments. D-Serine, produced by the enzyme serine racemase (SR) in the brain, functions as an endogenous co-agonist at the glycine-binding site of N-methyl-D-aspartate receptor (NMDAR), has been implicated in the pathophysiological progression of AD.</p><p><strong>Objectives: </strong>Evidence regarding the understanding of the role and dynamic modulation of D-serine during AD progression remains controversial. This literature review aims to offer novel research directions for studying the functions and metabolisms of D-serine in AD brains.</p><p><strong>Methods: </strong>We searched PubMed, using D-serine/SR and AD as keywords. Studies related to NMDAR dysfunction, neuronal excitotoxicity, D-serine dynamic changes and inflammatory response were included.</p><p><strong>Results: </strong>This review primarily discusses: (i) Aβ oligomers' role in NMDAR dysregulation, and the subsequent synaptic dysfunction and neuronal damage in AD, (ii) D-serine's role in NMDAR-elicited excitotoxicity, and (iii) the involvement of D-serine and SR in AD-related inflammatory pathological progression.</p><p><strong>Conclusion: </strong>We also presented supposed metabolism and dynamic changes of D-serine during AD progression and hypothesized that: (i) the possible modulation of D-serine levels or SR expression as an effective method of alleviating neurotoxicity during AD pathophysiological progression, and (ii) the dynamic changes of D-serine levels in AD brains possibly resulting from complex processes.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 7","pages":"485-493"},"PeriodicalIF":1.8000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":"{\"title\":\"Complex Processes Underlying the Dynamic Changes of D-serine Levels in AD Brains.\",\"authors\":\"Xiance Ni, Hisashi Mori\",\"doi\":\"10.2174/1567205019666220328123048\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular β-amyloid (Aβ) plaques and cognitive impairments. 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引用次数: 3
摘要
背景:阿尔茨海默病(AD)是一种以细胞外β-淀粉样蛋白(a β)斑块和认知障碍为特征的神经退行性疾病。脑内丝氨酸消旋酶(SR)产生的d -丝氨酸作为n -甲基- d -天冬氨酸受体(NMDAR)甘氨酸结合位点的内源性协同激动剂，参与了AD的病理生理进展。目的:关于d -丝氨酸在AD进展过程中的作用和动态调节的理解证据仍然存在争议。本综述旨在为研究d -丝氨酸在AD脑内的功能和代谢提供新的研究方向。方法:检索PubMed，以D-serine/SR和AD为关键词。包括与NMDAR功能障碍、神经元兴奋性毒性、d -丝氨酸动态变化和炎症反应相关的研究。结果:本综述主要讨论:(i) Aβ低聚物在AD中NMDAR失调中的作用，以及随后的突触功能障碍和神经元损伤，(ii) d -丝氨酸在NMDAR引起的兴奋性毒性中的作用，以及(iii) d -丝氨酸和SR在AD相关炎症病理进展中的作用。结论:我们还提出了AD进展过程中d -丝氨酸的代谢和动态变化，并假设:(i) AD病理生理进展过程中d -丝氨酸水平或SR表达的调节可能是缓解神经毒性的有效方法，以及(ii) AD大脑中d -丝氨酸水平的动态变化可能是由复杂的过程引起的。
Complex Processes Underlying the Dynamic Changes of D-serine Levels in AD Brains.
Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular β-amyloid (Aβ) plaques and cognitive impairments. D-Serine, produced by the enzyme serine racemase (SR) in the brain, functions as an endogenous co-agonist at the glycine-binding site of N-methyl-D-aspartate receptor (NMDAR), has been implicated in the pathophysiological progression of AD.
Objectives: Evidence regarding the understanding of the role and dynamic modulation of D-serine during AD progression remains controversial. This literature review aims to offer novel research directions for studying the functions and metabolisms of D-serine in AD brains.
Methods: We searched PubMed, using D-serine/SR and AD as keywords. Studies related to NMDAR dysfunction, neuronal excitotoxicity, D-serine dynamic changes and inflammatory response were included.
Results: This review primarily discusses: (i) Aβ oligomers' role in NMDAR dysregulation, and the subsequent synaptic dysfunction and neuronal damage in AD, (ii) D-serine's role in NMDAR-elicited excitotoxicity, and (iii) the involvement of D-serine and SR in AD-related inflammatory pathological progression.
Conclusion: We also presented supposed metabolism and dynamic changes of D-serine during AD progression and hypothesized that: (i) the possible modulation of D-serine levels or SR expression as an effective method of alleviating neurotoxicity during AD pathophysiological progression, and (ii) the dynamic changes of D-serine levels in AD brains possibly resulting from complex processes.
期刊介绍：
Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer''s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ''bird''s-eye view'' of the current state of Alzheimer''s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
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