ArticleMolecular and cellular biochemistry2009
The role of alpha-synuclein in brain lipid metabolism: a downstream impact on brain inflammatory response.
Article in Molecular and cellular biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- Parkinson disease is a fatty acidopathy.Nature reviews. Neurology · 2025Review
- Druggability of Sodium Calcium Exchanger (NCX): Challenges and Recent Development.International journal of molecular sciences · 2025Review
- Preclinical assessment of a ganglioside-targeted therapy for Parkinson's disease with the first-in-class adaptive peptide AmyP53.Scientific reports · 2025Article
- Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes.Cell reports · 2024Article
- Research progress on intranasal treatment for Parkinson's disease.Neuroprotection (Chichester, England) · 2024Review
- Integration of selective sweeps across the sheep genome: understanding the relationship between production and adaptation traits.Genetics, selection, evolution : GSE · 2024Article
- The potential role of cholesterol in Parkinson's disease neuropathology: perpetrator or victim.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Review
- Innovative treatment targeting gangliosides aimed at blocking the formation of neurotoxic α-synuclein oligomers in Parkinson's disease.Glycoconjugate journal · 2022Review
- Potential value of cerebrospinal fluid α-synuclein in the identification of postoperative delirium undergoing knee/hip arthroplasty: The perioperative neurocognitive disorder and biomarker lifestyle study.Frontiers in neuroscience · 2022Article
- Lipotoxicity Downstream of α-Synuclein Imbalance: A Relevant Pathomechanism in Synucleinopathies?Biomolecules · 2021Review
- Ncx3-Induced Mitochondrial Dysfunction in Midbrain Leads to Neuroinflammation in Striatum of A53t-α-Synuclein Transgenic Old Mice.International journal of molecular sciences · 2021Article
- Triple-Knockout, Synuclein-Free Mice Display Compromised Lipid Pattern.Molecules (Basel, Switzerland) · 2021Article
- Neutral lipids as early biomarkers of cellular fate: the case of α-synuclein overexpression.Cell death & disease · 2021Article
- Advances of Mechanisms-Related Metabolomics in Parkinson's Disease.Frontiers in neuroscience · 2021Review
- An Emerging Role for Phosphoinositides in the Pathophysiology of Parkinson's Disease.Journal of Parkinson's disease · 2021Review
- Mitochondria-Microbiota Interaction in Neurodegeneration.Frontiers in aging neuroscience · 2021Review
- α-Synuclein Translocates to the Nucleus to Activate Retinoic-Acid-Dependent Gene Transcription.iScience · 2020Article
- Recent advances and perspectives of metabolomics-based investigations in Parkinson's disease.Molecular neurodegeneration · 2019Review
- Lipid-Binding Proteins in Brain Health and Disease.Frontiers in neurology · 2019Review
- Lipids at the Crossroad of α-Synuclein Function and Dysfunction: Biological and Pathological Implications.Frontiers in cellular neuroscience · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Alpha-synuclein (Snca) is an abundant small cytosolic protein (140 amino acids) that is expressed in the brain, although its physiological role is poorly defined. Consistent with its ubiquitous distribution in the brain, we and others have established a role for Snca in brain lipid metabolism and downstream events such as neuroinflammation. In astrocytes, Snca is important for fatty acid uptake and trafficking, where its deletion decreases 16:0 and 20:4n-6 uptake and alters targeting to specific lipid pools. Although Snca has no impact on 22:6n-3 uptake into astrocytes, it is important for its targeting to lipid pools. Similar results for fatty acid uptake from the plasma are seen in studies using whole mice coupled with steady-state kinetic modeling. We demonstrate in gene-ablated mice a significant reduction in the incorporation rate of 20:4n-6 into brain phospholipid pools due to reduced recycling of 20:4n-6 through the ER-localized long-chain acyl-CoA synthetases (Acsl). This reduction results in a compensatory increase in the incorporation rate of 22:6n-3 into brain phospholipids. Snca is also important for brain and astrocyte cholesterol metabolism, where its deletion results in an elevation of cholesterol and cholesteryl esters. This increase may be due to the interaction of Snca with membrane-bound enzymes involved in lipid metabolism such as Acsl. Snca is critical in modulating brain prostanoid formation and microglial activities. In the absence of Snca, microglia are basally activated and demonstrate increased proinflammatory cytokine secretion. Thus, Snca, through its modulation of brain lipid metabolism, has a critical role in brain inflammatory responses.
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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.