{"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. 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":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Alzheimer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1567205019666220328123048","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 3
Abstract
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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