ArticleHuman molecular genetics2017
NCEH-1 modulates cholesterol metabolism and protects against α-synuclein toxicity in a C. elegans model of Parkinson's disease.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Article
- Ubiquitin Proteasome System Components, RAD23A and USP13, Modulate TDP-43 Solubility and Neuronal Toxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- STAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling.iScience · 2025Article
- Visualize neuronal membrane cholesterol with split-fluorescent protein tagged YDQA sensor.Journal of lipid research · 2025Article
- Circadian rhythm disruptions associated with opioid use disorder in synaptic proteomes of human dorsolateral prefrontal cortex and nucleus accumbens.Molecular psychiatry · 2023Article
- Integrated regulation of dopaminergic and epigenetic effectors of neuroprotection in Parkinson's disease models.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Lipid metabolism and ageing in Caenorhabditis elegans: a complex interplay.Biogerontology · 2022Review
- KIAA1363-A Multifunctional Enzyme in Xenobiotic Detoxification and Lipid Ester Hydrolysis.Metabolites · 2022Review
- A multi-omics study to characterize the transdifferentiation of human dermal fibroblasts to osteoblast-like cells.Frontiers in molecular biosciences · 2022Article
- Caenorhabditis elegans for rare disease modeling and drug discovery: strategies and strengths.Disease models & mechanisms · 2021Review
- Connecting Cholesterol Efflux Factors to Lung Cancer Biology and Therapeutics.International journal of molecular sciences · 2021Review
- Alteration in the Cerebrospinal Fluid Lipidome in Parkinson's Disease: A Post-Mortem Pilot Study.Biomedicines · 2021Article
- Modeling neurodegeneration inDisease models & mechanisms · 2020Review
- Cholesterol-binding protein TSPO2 coordinates maturation and proliferation of terminally differentiating erythroblasts.The Journal of biological chemistry · 2020Article
- Article
- Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in C. elegans.Cell reports · 2020Article
- The Role of Lipids in Parkinson's Disease.Cells · 2019Review
- Neuronal calcineurin transcriptional targets parallel changes observed in Alzheimer disease brain.Journal of neurochemistry · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Parkinson's disease (PD) is an aging-associated neurodegenerative disease affecting millions worldwide. Misfolding, oligomerization and accumulation of the human α-synuclein protein is a key pathological hallmark of PD and is associated with the progressive loss of dopaminergic neurons over the course of aging. Lifespan extension via the suppression of IGF-1/insulin-like signaling (IIS) offers a possibility to retard disease onset through induction of metabolic changes that provide neuroprotection. The nceh-1 gene of Caenorhabditis elegans encodes an ortholog of neutral cholesterol ester hydrolase 1 (NCEH-1), an IIS downstream protein that was identified in a screen as a modulator of α-synuclein accumulation in vivo. The mechanism whereby cholesterol metabolism functionally impacts neurodegeneration induced by α-synuclein is undefined. Here we report that NCEH-1 protects dopaminergic neurons from α-synuclein-dependent neurotoxicity in C. elegans via a mechanism that is independent of lifespan extension. We discovered that the presence of cholesterol, LDLR-mediated cholesterol endocytosis, and cholesterol efflux are all essential to NCEH-1-mediated neuroprotection. In protecting from α-synuclein neurotoxicity, NCEH-1 also stimulates cholesterol-derived neurosteroid formation and lowers cellular reactive oxygen species in mitochondria. Collectively, this study augments our understanding of how cholesterol metabolism can modulate a neuroprotective mechanism that attenuates α-synuclein neurotoxicity, thereby pointing toward regulation of neuronal cholesterol turnover as a potential therapeutic avenue for PD.
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