ArticleThe Journal of clinical investigation2024
The NR4A2/VGF pathway fuels inflammation-induced neurodegeneration via promoting neuronal glycolysis.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Comprehensive Meta-Analysis of Differentially Expressed Proteins in Cerebrospinal Fluid Associated with Multiple Sclerosis.International journal of molecular sciences · 2025Pooled it
- Article
- Associations of cerebrospinal fluid measures of synaptic function with white matter microstructure and cognition in older adults.Frontiers in aging neuroscience · 2026Article
- Review
- VGF AQEE- and GGEE-peptides differentiate between dementia types.Journal of neurology · 2025Article
- Glia inflammation and cell death pathways drive disease progression in preclinical and early AD.EMBO molecular medicine · 2025Article
- Early Dopaminergic Dysfunction Induces PRO-VGF Changes in Blood and Brain of Rats with Alpha-Synuclein Overexpression.Neurochemical research · 2025Article
- Identification and Validation of Inverse Agonists for Nuclear Receptor Subfamily 4 Group A Member 2.ACS omega · 2025Article
- VGF and Its Derived Peptides in Amyotrophic Lateral Sclerosis.Brain sciences · 2025Review
- Review
Corrections and comments
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Authors and funding
25 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A disturbed balance between excitation and inhibition (E/I balance) is increasingly recognized as a key driver of neurodegeneration in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. To understand how chronic hyperexcitability contributes to neuronal loss in MS, we transcriptionally profiled neurons from mice lacking inhibitory metabotropic glutamate signaling with shifted E/I balance and increased vulnerability to inflammation-induced neurodegeneration. This revealed a prominent induction of the nuclear receptor NR4A2 in neurons. Mechanistically, NR4A2 increased susceptibility to excitotoxicity by stimulating continuous VGF secretion leading to glycolysis-dependent neuronal cell death. Extending these findings to people with MS (pwMS), we observed increased VGF levels in serum and brain biopsies. Notably, neuron-specific deletion of Vgf in a mouse model of MS ameliorated neurodegeneration. These findings underscore the detrimental effect of a persistent metabolic shift driven by excitatory activity as a fundamental mechanism in inflammation-induced neurodegeneration.
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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 Socratic graph.