ArticleNeurobiology of disease2019
Neurotoxic astrocytes express the d-serine synthesizing enzyme, serine racemase, in Alzheimer's disease.
Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 3 of them syntheses that pooled it.
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Who cites it
48 citing papers in PubMed, 3 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Roles of neuropathology-associated reactive astrocytes: a systematic review.Acta neuropathologica communications · 2023Pooled it
- Systematic review of human post-mortem immunohistochemical studies and bioinformatics analyses unveil the complexity of astrocyte reaction in Alzheimer's disease.Neuropathology and applied neurobiology · 2022Pooled it
- The Role of Astrocytes in Synapse Loss in Alzheimer's Disease: A Systematic Review.Frontiers in cellular neuroscience · 2022Pooled it
- Advances in the role of astrocytes in glioma progression and therapy.Acta pharmacologica Sinica · 2026Review
- Entorhinal Astrocyte Transplants Restore Spatial Exploration and Alleviate Amyloid-Beta Pathology in Alzheimer's Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Biomolecular and cellular chirality: Novel diagnostic perspectives for diseases.APL bioengineering · 2026Review
- Novel drug treatments for schizophrenia.Nature reviews. Drug discovery · 2026Review
- APOE-ε4 genotype and western diet synergistically aggravate synaptic dysfunction in Alzheimer's disease via D-serine disruption.Alzheimer's research & therapy · 2026Article
- Microglial serine racemase knockout alleviates Alzheimer-like neuropathology and behavioral deficit via lactylation-mediated anti-inflammation.Communications biology · 2026Article
- D-serine: A Multitalented Neuromodulator in Brain Function, Systemic Homeostasis, and Disease.Cellular and molecular neurobiology · 2026Review
- The Role of Astrocytes in Synaptic Dysfunction and Memory Deficits in Alzheimer's Disease.Biomolecules · 2025Review
- Early involvement of D-serine in β-amyloid-dependent pathophysiology.Cellular and molecular life sciences : CMLS · 2025Article
- Age- and Sex-Specific Regulation of Serine Racemase in the Retina of an Alzheimer's Disease Mouse.Investigative ophthalmology & visual science · 2025Article
- Glucocorticoid-Dependent Retinal Degeneration and Vision Impairment in Mice Susceptible to Prenatal Stress-Induced Behavioral Abnormalities.Cellular and molecular neurobiology · 2024Article
- Associations of human blood metabolome with optic neurodegenerative diseases: a bi-directionally systematic mendelian randomization study.Lipids in health and disease · 2024Article
- Astrocytes: The Stars in Neurodegeneration?Biomolecules · 2024Review
- Disease-Associated Neurotoxic Astrocyte Markers in Alzheimer Disease Based on Integrative Single-Nucleus RNA Sequencing.Cellular and molecular neurobiology · 2024Article
- Microglial ferroptotic stress causes non-cell autonomous neuronal death.Molecular neurodegeneration · 2024Article
- Gene Expression at the Tripartite Synapse: Bridging the Gap Between Neurons and Astrocytes.Advances in neurobiology · 2024Review
- Astrocyte-Neuron Interactions in Alzheimer's Disease.Advances in neurobiology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Although β-amyloid plaques are a well-recognized hallmark of Alzheimer's disease (AD) neuropathology, no drugs reducing amyloid burden have shown efficacy in clinical trials, suggesting that once AD symptoms emerge, disease progression becomes independent of Aβ production. Reactive astrocytes are another neuropathological feature of AD, where there is an emergence of neurotoxic (A1) reactive astrocytes. We find that serine racemase (SR), the neuronal enzyme that produces the N-methyl-d-aspartate receptor (NMDAR) co-agonist d-serine, is robustly expressed in A1-reactive neurotoxic astrocytes in the hippocampus and entorhinal cortex of AD subjects and an AD rat model. Furthermore, we observe intracellular signaling changes consistent with increased extra-synaptic NMDAR activation, excitotoxicity and decreased neuronal survival. Thus, reducing neurotoxic d-serine release from A1 inflammatory astrocytes could have therapeutic benefit for mild to advanced AD, when anti-amyloid strategies are ineffective.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.