ArticlePloS one2017
α-Synuclein increases β-amyloid secretion by promoting β-/γ-secretase processing of APP.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- CSF α-synuclein seed amplification assay positivity identifies a distinct soluble amyloid-β profile linked to fibrillar amyloid burden and structural neurodegeneration.Research square · 2026Article
- The Potential Regulators of Amyloidogenic Pathway of APP Processing in Alzheimer's Disease.Biomedicines · 2025Review
- Identification of novel risk genes for Alzheimer's disease by integrating genetics from hippocampus.Scientific reports · 2024Article
- Pathological Involvement of Protein Phase Separation and Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Review
- α-Synuclein oligomers and fibrils: partners in crime in synucleinopathies.Neural regeneration research · 2023Article
- Novel systemic delivery of a peptide-conjugated antisense oligonucleotide to reduce α-synuclein in a mouse model of Alzheimer's disease.Neurobiology of disease · 2023Article
- Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity.iScience · 2023Article
- Review
- Overexpression of alpha synuclein disrupts APP and Endolysosomal axonal trafficking in a mouse model of synucleinopathy.Neurobiology of disease · 2023Article
- Hippocampal Reduction of α-Synuclein via RNA Interference Improves Neuropathology in Alzheimer's Disease Mice.Journal of Alzheimer's disease : JAD · 2023Article
- The old second messenger cAMP teams up with novel cell death mechanisms: potential translational therapeutical benefit for Alzheimer's disease and Parkinson's disease.Frontiers in physiology · 2023Review
- Oligomerization by co-assembly of β-amyloid and α-synuclein.Frontiers in molecular biosciences · 2023Review
- Plasma biomarkers inclusive of α-synuclein/amyloid-beta40 ratio strongly correlate with Mini-Mental State Examination score in Parkinson's disease and predict cognitive impairment.Journal of neurology · 2022Article
- Influence of TiOMaterials (Basel, Switzerland) · 2022Article
- Ingenuity pathway analysis ofFrontiers in molecular neuroscience · 2022Article
- N-Acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 21.Scientific reports · 2021Article
- High-throughput generation of midbrain dopaminergic neuron organoids from reporter human pluripotent stem cells.STAR protocols · 2021Article
- Recent Insights into the Interplay of Alpha-Synuclein and Sphingolipid Signaling in Parkinson's Disease.International journal of molecular sciences · 2021Review
- Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.Chemical reviews · 2021Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α-Synuclein misfolding and aggregation is often accompanied by β-amyloid deposition in some neurodegenerative diseases. We hypothesised that α-synuclein promotes β-amyloid production from APP. β-Amyloid levels and APP amyloidogenic processing were investigated in neuronal cell lines stably overexpressing wildtype and mutant α-synuclein. γ-Secretase activity and β-secretase expression were also measured. We show that α-synuclein expression induces β-amyloid secretion and amyloidogenic processing of APP in neuronal cell lines. Certain mutations of α-synuclein potentiate APP amyloidogenic processing. γ-Secretase activity was not enhanced by wildtype α-synuclein expression, however β-secretase protein levels were induced. Furthermore, a correlation between α-synuclein and β-secretase protein was seen in rat brain striata. Iron chelation abolishes the effect of α-synuclein on neuronal cell β-amyloid secretion, whereas overexpression of the ferrireductase enzyme Steap3 is robustly pro-amyloidogenic. We propose that α-synuclein promotes β-amyloid formation by modulating β-cleavage of APP, and that this is potentially mediated by the levels of reduced iron and oxidative stress.
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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.