ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
A pathologic cascade leading to synaptic dysfunction in alpha-synuclein-induced neurodegeneration.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers, 1 of them a synthesis that pooled it.
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Who cites it
217 citing papers in PubMed, 1 synthesis or guideline pooled it, 359 citations in OpenAlex.
- The Effect of Aggregated Alpha Synuclein on Synaptic and Axonal Proteins in Parkinson's Disease-A Systematic Review.Biomolecules · 2022Pooled it
- Increased Expression of α-Synuclein Impairs Trafficking of the Essential SNARE Protein Synaptobrevin-2.Journal of neurochemistry · 2026Article
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Gut-initiated alpha synuclein fibrils drive parkinsonism phenotypes: temporal mapping of REM sleep behavior disorder-like and other non-motor symptoms.Translational neurodegeneration · 2026Article
- R5 and R7 positions on fluoroquinolone scaffolds drive F-actin filament disruption.Scientific reports · 2026Article
- Alpha-Synuclein Dynamics in Cerebral Ischemia.ASN neuro · 2026Review
- Parkinson's Disease: From Bench to Bedside-Advancements in Diagnosis and Therapeutics using Pharmacogenomic Approach.Current gene therapy · 2026Review
- Phytoconstituents as Potential Therapeutics against Enzymatic Targets for Neurodegenerative Diseases.Current protein & peptide science · 2026Review
- Synaptic Vesicle Disruption in Parkinson's Disease: Dual Roles of α-Synuclein and Emerging Therapeutic Targets.Brain sciences · 2025Review
- Optogenetic-induced α-synuclein accumulation reveals early synaptic dysfunction in experimental models of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- Early Dopaminergic Dysfunction Induces PRO-VGF Changes in Blood and Brain of Rats with Alpha-Synuclein Overexpression.Neurochemical research · 2025Article
- Pathogenic mechanism underlying parkinsonism induced by neurotoxicants (MPTP and 6-hydroxydopamine) and α-synuclein: a unifying hypothesis.Journal of molecular cell biology · 2025Review
- Acute introduction of monomeric or multimeric α-synuclein induces distinct impacts on synaptic vesicle trafficking at lamprey giant synapses.The Journal of physiology · 2025Article
- Glutamatergic synaptic resilience to overexpressed human alpha-synuclein.NPJ Parkinson's disease · 2025Article
- Experimental and computational insights into the therapeutic mechanisms of resveratrol in a Drosophila α-synuclein model of Parkinson's disease.Scientific reports · 2025Article
- α-Synuclein interacts directly with AP2 and regulates its binding to synaptic membranes.The Journal of biological chemistry · 2025Article
- Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy.Nature communications · 2025Article
- Live-cell quantification reveals viscoelastic regulation of synapsin condensates by α-synuclein.Science advances · 2025Article
- PET tracer development for imaging α-synucleinopathies.Archives of pharmacal research · 2025Review
157 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Several neurodegenerative diseases are typified by intraneuronal alpha-synuclein deposits, synaptic dysfunction, and dementia. While even modest alpha-synuclein elevations can be pathologic, the precise cascade of events induced by excessive alpha-synuclein and eventually culminating in synaptotoxicity is unclear. To elucidate this, we developed a quantitative model system to evaluate evolving alpha-synuclein-induced pathologic events with high spatial and temporal resolution, using cultured neurons from brains of transgenic mice overexpressing fluorescent-human-alpha-synuclein. Transgenic alpha-synuclein was pathologically altered over time and overexpressing neurons showed striking neurotransmitter release deficits and enlarged synaptic vesicles; a phenotype reminiscent of previous animal models lacking critical presynaptic proteins. Indeed, several endogenous presynaptic proteins involved in exocytosis and endocytosis were undetectable in a subset of transgenic boutons ("vacant synapses") with diminished levels in the remainder, suggesting that such diminutions were triggering the overall synaptic pathology. Similar synaptic protein alterations were also retrospectively seen in human pathologic brains, highlighting potential relevance to human disease. Collectively the data suggest a previously unknown cascade of events where pathologic alpha-synuclein leads to a loss of a number of critical presynaptic proteins, thereby inducing functional synaptic deficits.
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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.