ArticleCell death & disease2025
PHGDH-mediated serine synthesis in astrocytes supports neuroinflammation by sustaining NADH level to promote histone acetylation.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Cross-tissue immune profiling of APOE ε4 reveals early dysregulation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Reduced Myocardial Serine Synthesis Impairs Functional, Metabolic, and Redox Adaptations to Cardiac Stress.bioRxiv : the preprint server for biology · 2026Article
- Astrocytic EAAT1 suppression by EV-ACLY underlies glutamate imbalance and cognitive impairment in POCD.Communications biology · 2026Article
- A Highly Efficient siRNA Transfection Method in Primary Cultured Cortical Neurons.Bio-protocol · 2026Article
- Therapeutic Efficacy of Curcumin Nanoparticles in Parkinson's Disease: An Integrated Analysis of Network Pharmacology, Experimental Validation, and Gut Microbiota.Drug design, development and therapy · 2026Article
- PHGDH-mediated serine synthesis reduces oligodendrocyte death by sustaining GSH and NADPH levels after brain ischemia.Frontiers in pharmacology · 2026Article
- Review
- Protein post-translational modifications in serine synthetic pathway: functions and molecular mechanisms.Cell communication and signaling : CCS · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Neuroinflammation contributes to the loss of dopamine neurons and motor dysfunctions in Parkinson's disease (PD). How cell metabolism regulates neuroinflammation by modulating epigenetic modifications is largely unknown. In this study, we found that the expression of phosphoglycerate dehydrogenase (PHGDH) which catalyzes the first step of the de novo serine synthesis pathway was mainly expressed in astrocytes and l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) injection triggered the upregulation of PHGDH in astrocytes in substantia nigra. PHGDH inhibition or knockdown reduced proinflammatory cytokine production in primary astrocytes after LPS (lipopolysaccharide) stimulation which was not due to suppressed inflammatory signaling transduction. Mechanistically, PHGDH promotes proinflammatory cytokine transcription by sustaining nicotinamide adenine dinucleotide (NADH) accumulation to facilitate histone acetylation of cytokine promoters. Moreover, PHGDH inhibition-induced inflammatory response decreased neurotoxicity in vitro and alleviated astrocytes-mediated neuroinflammation and neurotoxicity in an MPTP mice model. This study reveals the role and mechanism of PHGDH-mediated serine synthesis in promoting the inflammatory response of astrocytes which may provide a potential target for neurological diseases involving neuroinflammation.
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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.