Complex Processes Underlying the Dynamic Changes of D-serine Levels in AD Brains
Xiance Ni1, Hisashi Mori1,2
1Graduate School of Innovative Life Science, University of Toyama, Toyama 930-0194, Japan.
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.
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