ArticleActa neuropathologica communications2016
High expression of α-synuclein in damaged mitochondria with PLA2G6 dysfunction.
Article in Acta neuropathologica communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Therapeutic Advances in Major NBIA Disorders: Current Strategies and Translational Challenges.Neurology international · 2026Review
- Lipid metabolism, remodelling and intercellular transfer in the CNS.Nature reviews. Neuroscience · 2025Review
- Role of Lipids in the Pathogenesis of Parkinson's Disease.International journal of molecular sciences · 2024Review
- Involvement of Mitochondria in Parkinson's Disease.International journal of molecular sciences · 2023Review
- RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS.Science advances · 2023Article
- Novel mutations and molecular pathways identified in patients with brain iron accumulation disorders.Neurogenetics · 2023Article
- Alpha synuclein modulates mitochondrial CaNPJ Parkinson's disease · 2023Article
- Phosphatidylinositol-3,4,5-trisphosphate interacts with alpha-synuclein and initiates its aggregation and formation of Parkinson's disease-related fibril polymorphism.Acta neuropathologica · 2023Article
- Molecular basis of unique specificity and regulation of group VIA calcium-independent phospholipase APharmacology & therapeutics · 2023Review
- Alpha Synuclein Modulates Mitochondrial CabioRxiv : the preprint server for biology · 2023Article
- Transcutaneous auricular vagus nerve stimulation in the treatment of disorders of consciousness: mechanisms and applications.Frontiers in neuroscience · 2023Review
- Cerebral Iron Deposition in Neurodegeneration.Biomolecules · 2022Review
- Mitochondrial Dysfunction in Parkinson's Disease: From Mechanistic Insights to Therapy.Frontiers in aging neuroscience · 2022Review
- Insights into Lewy body disease from rare neurometabolic disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Review
- Animal Models of Autosomal Recessive Parkinsonism.Biomedicines · 2021Review
- Lipids, lysosomes and mitochondria: insights into Lewy body formation from rare monogenic disorders.Acta neuropathologica · 2021Review
- Neutral lipids as early biomarkers of cellular fate: the case of α-synuclein overexpression.Cell death & disease · 2021Article
- Fatty Acid-Binding Protein 3 Expression in the Brain and Skin in Human Synucleinopathies.Frontiers in aging neuroscience · 2021Article
- Pluripotent Stem Cell Derived Neurons as In Vitro Models for Studying Autosomal Recessive Parkinson's Disease (ARPD): PLA2G6 and Other Gene Loci.Advances in experimental medicine and biology · 2021Article
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To clarify the role of α-synuclein (αSyn) in neuronal membrane remodeling, we analyzed the expression of αSyn in neurons with a dysfunction of PLA2G6, which is indispensable for membrane remodeling. αSyn/phosphorylated-αSyn (PαSyn) distribution and neurodegeneration were quantitatively estimated in PLA2G6-knockout (KO) mice, which demonstrate marked mitochondrial membrane degeneration. We also assessed the relationship between αSyn deposits and mitochondria in brain tissue from patients with PLA2G6-associated neurodegeneration (PLAN) and Parkinson's disease (PD), and quantitatively examined Lewy bodies (LBs) and neurons. The expression level of αSyn was elevated in PLA2G6-knockdown cells and KO mouse neurons. Strong PαSyn expression was observed in neuronal granules in KO mice before onset of motor symptoms. The granules were mitochondrial outer membrane protein (TOM20)-positive. Ultramicroscopy revealed that PαSyn-positive granules were localized to mitochondria with degenerated inner membranes. After symptom onset, TOM20-positive granules were frequently found in ubiquitinated spheroids, where PαSyn expression was low. Axons were atrophic, but the neuronal loss was not evident in KO mice. In PLAN neurons, small PαSyn-positive inclusions with a TOM20-positive edge were frequently observed and clustered into LBs. The surfaces of most LBs were TOM20-positive in PLAN and TOM20-negative in PD brains. The high proportion of LB-bearing neurons and the preserved neuronal number in PLAN suggested long-term survival of LB-bearing neurons. Elevated expression of αSyn/PαSyn in mitochondria appears to be the early response to PLA2G6-deficiency in neurons. The strong affinity of αSyn for damaged mitochondrial membranes may promote membrane stabilization of mitochondria and neuronal survival in neurons.
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