ArticleScientific reports2018
Lipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Trans-Vitisin B Targets Neuroinflammation, Oxidative Stress, and Tau Pathology to Improve Behavioral Outcomes in a Mouse Model of Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2026Article
- APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons.PNAS nexus · 2026Article
- APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons.bioRxiv : the preprint server for biology · 2025Article
- Upstream lipid and metabolic systems are potential causes of Alzheimer's disease, Parkinson's disease and dementias.The FEBS journal · 2024Review
- Review
- Parkinson-causing mutations in LRRK2 impair the physiological tetramerization of endogenous α-synuclein in human neurons.NPJ Parkinson's disease · 2022Article
- Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach.NPJ Parkinson's disease · 2021Article
- Neuropathology of SCA34 showing widespread oligodendroglial pathology with vacuolar white matter degeneration: a case study.Acta neuropathologica communications · 2021Article
- The Role of Cholesterol in α-Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021Review
- Vesicle trafficking and lipid metabolism in synucleinopathy.Acta neuropathologica · 2021Review
- Fibroblasts from idiopathic Parkinson's disease exhibit deficiency of lysosomal glucocerebrosidase activity associated with reduced levels of the trafficking receptor LIMP2.Molecular brain · 2021Article
- Cell type-specific lipid storage changes in Parkinson's disease patient brains are recapitulated by experimental glycolipid disturbance.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Upregulating β-hexosaminidase activity in rodents prevents α-synuclein lipid associations and protects dopaminergic neurons from α-synuclein-mediated neurotoxicity.Acta neuropathologica communications · 2020Article
- Immunotherapies for Aging-Related Neurodegenerative Diseases-Emerging Perspectives and New Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
- Glucocerebrosidase: Functions in and Beyond the Lysosome.Journal of clinical medicine · 2020Review
- Cerebrospinal fluid proteomics implicates the granin family in Parkinson's disease.Scientific reports · 2020Article
- Proteostasis of α-Synuclein and Its Role in the Pathogenesis of Parkinson's Disease.Frontiers in cellular neuroscience · 2020Review
- Parkinson's disease: proteinopathy or lipidopathy?NPJ Parkinson's disease · 2020Review
- Reduced sphingolipid hydrolase activities, substrate accumulation and ganglioside decline in Parkinson's disease.Molecular neurodegeneration · 2019Article
- Lipid and immune abnormalities causing age-dependent neurodegeneration and Parkinson's disease.Journal of neuroinflammation · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
This report demonstrates insoluble alpha-synuclein (aSYN)+ aggregates in human sporadic Parkinson's disease (PD) midbrain that are linearly correlated with loss of glucocerebrosidase (GCase) activity. To identify early protein-lipid interactions that coincide with loss of lipid homeostasis, an aging study was carried out in mice with age-dependent reductions in GCase function. The analysis identified aberrant lipid-association by aSYN and hyperphosphorylated Tau (pTau) in a specific subset of neurotransmitter-containing, Secretogranin II (SgII)+ large, dense-core vesicles (LDCVs) responsible for neurotransmission of dopamine and other monoamines. The lipid vesicle-accumulation was concurrent with loss of PSD-95 suggesting synaptic destabilization. aSYN overexpression in the absence of lipid deregulation did not recapitulate the abnormal association with SgII+ vesicles. These results show lipid-dependent changes occur with age in neuronal vesicular membrane compartments that accumulate lipid-stabilized aSYN and pTau.
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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.