ArticleProceedings of the National Academy of Sciences of the United States of America2020
Cell type-specific lipid storage changes in Parkinson's disease patient brains are recapitulated by experimental glycolipid disturbance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Convergent Astrocytic Failure in Parkinson's Disease: A System-Level Model of Pathogenesis and Treatment.Molecular neurobiology · 2026Review
- Article
- Reduction of Lipid Droplets Modulates the Injury Response and Enhances CNTF-Induced Axon Regeneration Following Optic Nerve Crush.Molecular neurobiology · 2026Article
- Lipid Metabolism in Central Nervous System Diseases: Pathological Mechanisms and Therapeutic Advances.CNS neuroscience & therapeutics · 2026Review
- Redox Molecules in Aging and Neurodegenerative Disorders.International journal of molecular sciences · 2026Review
- The role of lipid metabolism in neuronal senescence.FEBS open bio · 2026Review
- A scalable human-zebrafish xenotransplantation model reveals gastrosome-mediated processing of dying neurons by human microglia.Communications biology · 2026Article
- APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons.PNAS nexus · 2026Article
- Chronic intermittent hypoxia increases Parkinson's disease susceptibility via PPARα-mediated lipid droplet-mitochondrial dysfunction.Theranostics · 2026Article
- Integrated Biofluid Proteomics Identified Dynamic Functional Biomarkers ofmedRxiv : the preprint server for health sciences · 2025Article
- Quantitative multi-metabolite imaging of Parkinson's disease using AI boosted molecular MRI.Npj imaging · 2025Article
- Microglial lipid droplets as therapeutic targets in age-related neurodegenerative diseases.npj aging · 2025Review
- Labile iron overload reprograms microglia and neurons for lipid droplet synthesis in the aging brain.bioRxiv : the preprint server for biology · 2025Article
- APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons.bioRxiv : the preprint server for biology · 2025Article
- The Mitochondrial-Astrocyte-Neuron Triad Hypothesis in Parkinson's Disease: A Toxic Feedback Loop of Metabolism, Aggregation, and Oxidative Stress.Neurochemical research · 2025Review
- Expanding our understanding of synucleinopathies: proteinopathy, proteinopenia, and lipidopathy.The FEBS journal · 2025Review
- Activated TBK1 promotes ACSL1-mediated microglia lipid droplet accumulation and neuroinflammation in Parkinson's disease.Journal of neuroinflammation · 2025Article
- Lipid metabolism in health and disease: Mechanistic and therapeutic insights for Parkinson's disease.Chinese medical journal · 2025Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Neurons are dependent on proper trafficking of lipids to neighboring glia for lipid exchange and disposal of potentially lipotoxic metabolites, producing distinct lipid distribution profiles among various cell types of the central nervous system. Little is known of the cellular distribution of neutral lipids in the substantia nigra (SN) of Parkinson's disease (PD) patients and its relationship to inflammatory signaling. This study aimed to determine human PD SN neutral lipid content and distribution in dopaminergic neurons, astrocytes, and microglia relative to age-matched healthy subject controls. The results show that while total neutral lipid content was unchanged relative to age-matched controls, the levels of whole SN triglycerides were correlated with inflammation-attenuating glycoprotein non-metastatic melanoma protein B (GPNMB) signaling in human PD SN. Histological localization of neutral lipids using a fluorescent probe (BODIPY) revealed that dopaminergic neurons and midbrain microglia significantly accumulated intracellular lipids in PD SN, while adjacent astrocytes had a reduced lipid load overall. This pattern was recapitulated by experimental in vivo inhibition of glucocerebrosidase activity in mice. Agents or therapies that restore lipid homeostasis among neurons, astrocytes, and microglia could potentially correct PD pathogenesis and disease progression.
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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.