Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.

Yulu He, Tingting Yi, Meixin Min, Ke Xu, Huan Lin, Rong Xu, Dan Deng, Xiaoping Xiao

Abstract readReview

In one paragraph

Review in Neuroscience bulletin, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Yulu HeGanzhou Key Laboratory for Drug Screening and Discovery, Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, China.

Tingting YiGanzhou Key Laboratory for Drug Screening and Discovery, Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, China.

Meixin MinGanzhou Key Laboratory for Drug Screening and Discovery, Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, China.

Ke XuGanzhou Key Laboratory for Drug Screening and Discovery, Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, China.

Huan LinGanzhou Key Laboratory for Drug Screening and Discovery, Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, China.

Rong XuThe First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.

Dan DengGannan Health Vocational College, Ganzhou, 341000, China.

Xiaoping XiaoGanzhou Key Laboratory for Drug Screening and Discovery, Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, China. xiaoxiaoping100@163.com.ORCID http://orcid.org/0000-0002-3343-8282

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This review illustrates how environmental stressors disrupt glutamate homeostasis via specific mechanisms: lead-induced thiol modification, manganese mediated yin yang 1 (YY1)-histone deacetylases (HDAC) repression, PM2.5-triggered microglia-astrocyte crosstalk, and advanced glycation end products (AGEs)-receptor for advanced glycation end products (RAGE)-nuclear factor kappa-B (NF-κB) signaling from high-sugar diets. Together with genetic susceptibility and pigment epithelium-derived factor (PEDF), these factors impair astrocytic glutamate uptake, promoting synaptic glutamate accumulation. Subsequent N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor overactivation triggers calcium overload, mitochondrial dysfunction, oxidative stress, and neuroinflammation-termed "degenerative excitotoxicity". Excitotoxicity manifests in Alzheimer's disease (amyloid-beta-excitatory amino acid transporter 2 (EAAT2) interplay), Parkinson's disease (subthalamic nucleus-driven excitatory storm), and amyotrophic lateral sclerosis (astrocytic failure versus neuronal cell-autonomous mechanisms). Future interventions need multi-target strategies, emerging technologies, and lifestyle modifications. This convergent framework offers a unified understanding linking environmental exposure to neurodegeneration and charts a roadmap toward mechanism-based prevention and treatment.

Indexed as

Alzheimer's diseaseAmyotrophic lateral sclerosisExcitotoxicityGlutamateNeurodegenerative diseasesParkinson's disease

Identifiers

PMID42274906

DOI10.1186/s13148-020-00864-y

What Socratic holds

Textmetadata

Read underepoch 390

Registered trials

None linked

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.