ArticleProceedings of the National Academy of Sciences of the United States of America2014
Phosphatidylethanolamine deficiency disrupts α-synuclein homeostasis in yeast and worm models of Parkinson disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 100 citations in OpenAlex.
- Condensate-driven triglyceride reduction links α-synuclein to mitochondrial dysfunction.EMBO reports · 2026Article
- Implications of mitochondrial phosphatidylethanolamine in neuronal health and neurodegeneration.Neural regeneration research · 2026Article
- Foldamers rescue synucleinopathy phenotypes in multiple in vitro and in vivo models.Science translational medicine · 2026Article
- In Vivo Screen of Parkinson's Disease GWAS Risk Genes IdentifiesThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Phosphatidylethanolamine modulates α-synuclein membrane-binding behavior.Biophysical journal · 2026Article
- Phospholipid biogenesis maintains neuronal integrity during aging and axon regeneration.Genetics · 2025Article
- Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy.Nature communications · 2025Article
- Investigating plasma lipid profiles in association with Parkinson's disease risk.NPJ Parkinson's disease · 2025Review
- Direct Current Stimulation (DCS) Modulates Lipid Metabolism and Intercellular Vesicular Trafficking in SHSY-5Y Cell Line: Implications for Parkinson's Disease.Journal of neurochemistry · 2025Article
- A pre-vaccination immune metabolic interplay determines the protective antibody response to a dengue virus vaccine.Cell reports · 2024Article
- Environmental risk factors provoke new thinking for prevention and treatment of dementia with Lewy bodies.Heliyon · 2024Review
- Protein mimetic 2D FAST rescues alpha synuclein aggregation mediated early and post disease Parkinson's phenotypes.Nature communications · 2024Article
- Plasma Amino Acid Profile in Children with Autism Spectrum Disorder in Southern China: Analysis of 110 Cases.Journal of autism and developmental disorders · 2024Article
- Article
- More than meets the eye in Parkinson's disease and other synucleinopathies: from proteinopathy to lipidopathy.Acta neuropathologica · 2023Review
- The Bidirectional Interplay of α-Synuclein with Lipids in the Central Nervous System and Its Implications for the Pathogenesis of Parkinson's Disease.International journal of molecular sciences · 2023Review
- Multiple tethers of organelle contact sites are involved in α-synuclein toxicity in yeast.Molecular biology of the cell · 2023Article
- Phospholipids, the Masters in the Shadows during Healing after Acute Myocardial Infarction.International journal of molecular sciences · 2023Review
- Use of invertebrates to model chemically induced parkinsonism-symptoms.Biochemical Society transactions · 2023Review
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphatidylserine decarboxylase, which is embedded in the inner mitochondrial membrane, synthesizes phosphatidylethanolamine (PE) and, in some cells, synthesizes the majority of this important phospholipid. Normal levels of PE can decline with age in the brain. Here we used yeast and worms to test the hypothesis that low levels of PE alter the homeostasis of the Parkinson disease-associated protein α-synuclein (α-syn). In yeast, low levels of PE in the phosphatidylserine decarboxylase deletion mutant (psd1Δ) cause decreased respiration, endoplasmic reticulum (ER) stress, a defect in the trafficking of the uracil permease, α-syn accumulation and foci, and a slow growth phenotype. Supplemental ethanolamine (ETA), which can be converted to PE via the Kennedy pathway enzymes in the ER, had no effect on respiration, whereas, in contrast, this metabolite partially eliminated ER stress, decreased α-syn foci formation, and restored growth close to that of wild-type cells. In Caenorhabditis elegans, RNAi depletion of phosphatidylserine decarboxylase in dopaminergic neurons expressing α-syn accelerates neurodegeneration, which supplemental ETA rescues. ETA fails to rescue this degeneration in worms that undergo double RNAi depletion of phosphatidylserine decarboxylase (psd-1) and choline/ETA phosphotransferase (cept-1), which encodes the last enzyme in the CDP-ETA Kennedy pathway. This finding suggests that ETA exerts its protective effect by boosting PE through the Kennedy pathway. Overall, a low level of PE causes ER stress, disrupts vesicle trafficking, and causes α-syn to accumulate; such cells likely die from a combination of ER stress and excessive accumulation of α-syn.
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