ArticleBiochemistry2006
Acyl-CoA synthetase activity links wild-type but not mutant alpha-synuclein to brain arachidonate metabolism.
Article in Biochemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 84 citations in OpenAlex.
- The diverse forms and roles of the neuronal endoplasmic reticulum.Nature reviews. Neuroscience · 2026Review
- Glycerol 3-phosphate acyltransferase exacerbates α-synuclein-induced toxicity by increasing lipid peroxidation.Nature communications · 2026Article
- Parkinson disease is a fatty acidopathy.Nature reviews. Neurology · 2025Review
- A crazy trio in Parkinson's disease: metabolism alteration, α-synuclein aggregation, and oxidative stress.Molecular and cellular biochemistry · 2025Review
- Identifying MSMO1, ELOVL6, AACS, and CERS2 related to lipid metabolism as biomarkers of Parkinson's disease.Scientific reports · 2024Article
- Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies.Metabolites · 2024Review
- Mapping the Research of Ferroptosis in Parkinson's Disease from 2013 to 2023: A Scientometric Review.Drug design, development and therapy · 2024Review
- 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
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- Lipotoxicity Downstream of α-Synuclein Imbalance: A Relevant Pathomechanism in Synucleinopathies?Biomolecules · 2021Review
- α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox.Cell & bioscience · 2021Review
- Parkinson's Disease-Related Genes and Lipid Alteration.International journal of molecular sciences · 2021Review
- The dysregulatedAging · 2021Article
- Neutral lipids as early biomarkers of cellular fate: the case of α-synuclein overexpression.Cell death & disease · 2021Article
- Crucial Role of FABP3 in αSyn-Induced Reduction of Septal GABAergic Neurons and Cognitive Decline in Mice.International journal of molecular sciences · 2021Article
- Diet and Exercise Training Influence Skeletal Muscle Long-Chain acyl-CoA Synthetases.Medicine and science in sports and exercise · 2020Article
- Intrinsically disordered proteins in synaptic vesicle trafficking and release.The Journal of biological chemistry · 2019Review
- Dysregulated Lipid Metabolism and Its Role in α-Synucleinopathy in Parkinson's Disease.Frontiers in neuroscience · 2019Review
- Landscape of Loci and Candidate Genes for Muscle Fatty Acid Composition in Pigs Revealed by Multiple Population Association Analysis.Frontiers in genetics · 2019Article
- Lipids at the Crossroad of α-Synuclein Function and Dysfunction: Biological and Pathological Implications.Frontiers in cellular neuroscience · 2019Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Because alpha-synuclein (Snca) has a role in brain lipid metabolism, we determined the impact that the loss of alpha-synuclein had on brain arachidonic acid (20:4n-6) metabolism in vivo using Snca-/- mice. We measured [1-(14)C]20:4n-6 incorporation and turnover kinetics in brain phospholipids using an established steady-state kinetic model. Liver was used as a negative control, and no changes were observed between groups. In Snca-/- brains, there was a marked reduction in 20:4n-6-CoA mass and in microsomal acyl-CoA synthetase (Acsl) activity toward 20:4n-6. Microsomal Acsl activity was completely restored after the addition of exogenous wild-type mouse or human alpha-synuclein, but not by A30P, E46K, and A53T forms of alpha-synuclein. Acsl and acyl-CoA hydrolase expression was not different between groups. The incorporation and turnover of 20:4n-6 into brain phospholipid pools were markedly reduced. The dilution coefficient lambda, which indicates 20:4n-6 recycling between the acyl-CoA pool and brain phospholipids, was increased 3.3-fold, indicating more 20:4n-6 was entering the 20:4n-6-CoA pool from the plasma relative to that being recycled from the phospholipids. This is consistent with the reduction in Acsl activity observed in the Snca-/- mice. Using titration microcalorimetry, we determined that alpha-synuclein bound free 20:4n-6 (Kd = 3.7 microM) but did not bind 20:4n-6-CoA. These data suggest alpha-synuclein is involved in substrate presentation to Acsl rather than product removal. In summary, our data demonstrate that alpha-synuclein has a major role in brain 20:4n-6 metabolism through its modulation of endoplasmic reticulum-localized acyl-CoA synthetase activity, although mutant forms of alpha-synuclein fail to restore this activity.
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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.