Affinage

SNCA

Alpha-synuclein · UniProt P37840

Length
140 aa
Mass
14.5 kDa
Annotated
2026-06-10
100 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNCA encodes alpha-synuclein, a natively unfolded, intrinsically disordered presynaptic protein that exists in solution as a mixture of rapidly equilibrating extended conformers lacking stable secondary structure or a hydrophobic core (PMID:8901511, PMID:9085269). In neurons it dynamically associates with synaptic vesicles and disperses upon membrane depolarization, linking its membrane interactions to neuronal activity (PMID:32788297), and it is loosely associated with plasma and endomembranes (PMID:9299413). Through its central NAC domain alpha-synuclein binds amyloid-beta peptides and promotes their aggregation, and this same aggregation-prone region drives its own conversion into amyloid fibrils (PMID:7568089); pathogenic missense mutations divergently tune this process, with H50Q accelerating and G51D slowing fibril formation while A30G locally perturbs the disordered structure to promote fibrillization (PMID:24984882, PMID:33617693). Cryo-EM of patient-derived filaments establishes that distinct disease-specific folds underlie the synucleinopathy spectrum, including a novel compact fold (residues 36–100) in juvenile-onset disease that cannot be reproduced by in vitro assembly of recombinant protein, implicating a non-proteinaceous cofactor (PMID:36847833). SNCA dosage is controlled at multiple regulatory layers: transcriptionally by the upstream NACP-Rep1 microsatellite, which recruits PARP-1 to repress transcription (PMID:15672325); epigenetically by DNA methylation at intron 1 and H3K4me3 at the promoter, both of which directly tune mRNA and protein levels (PMID:30266652, PMID:33428332); and post-transcriptionally by miR-30b binding the 3'-UTR (PMID:32154657). Alpha-synuclein is cleared chiefly through the autophagy-lysosomal pathway, requiring lysosomal cathepsin D for degradation (PMID:35287553) and a BAG3–HSP70–p62 complex that routes it into macroautophagy (PMID:28941726); this clearance is impaired by GBA loss acting through PPP2A inactivation (PMID:26378614) and by ABL1 kinase activation (PMID:23787811), while autophagy blockade redirects oligomeric species to exosomal secretion (PMID:25484190).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 High

    Established that alpha-synuclein physically engages amyloid-beta through its NAC domain and promotes Aβ aggregation, defining the aggregation-prone module central to its later disease biology.

    Evidence Filter-binding, deletion mutagenesis (NAC-deleted mutant), and aggregation assays with recombinant protein

    PMID:7568089

    Open questions at the time
    • Did not establish whether NAC-mediated self-assembly occurs under physiological conditions
    • No structural model of the bound complex
  2. 1996 High

    Resolved the basic biophysical nature of the protein, showing it is natively unfolded rather than globular, which reframed how its function and aggregation must be understood.

    Evidence Analytical ultracentrifugation, CD, FTIR, UV on purified protein, confirmed by independent gel-filtration/proteolysis study (1997)

    PMID:8901511 PMID:9085269

    Open questions at the time
    • Did not address conformations adopted upon membrane or partner binding
    • No in-cell conformational data
  3. 1997 Medium

    Provided the first subcellular localization, placing the protein at plasma and endomembranes and secretory granule membranes.

    Evidence Immunogold electron microscopy of human platelets

    PMID:9299413

    Open questions at the time
    • Single localization method without neuronal context
    • Did not define membrane-binding determinants
  4. 2001 Medium

    Identified the upstream NACP-Rep1 microsatellite as a cis-regulatory modulator of SNCA transcription, providing a dosage-control mechanism relevant to expression-driven disease.

    Evidence Luciferase reporter assays with deletion and allele-specific constructs in neuroblastoma cells

    PMID:11751692

    Open questions at the time
    • Did not identify the trans-acting factor
    • Cell-culture reporter context only
  5. 2005 High

    Named PARP-1 as the trans-acting factor binding NACP-Rep1 to repress SNCA, mechanistically completing the upstream regulatory model.

    Evidence Rep1 pulldown/MS, EMSA, ChIP, PARP-1 inhibition, and endogenous mRNA qRT-PCR in SH-SY5Y cells

    PMID:15672325

    Open questions at the time
    • Did not establish in vivo relevance in brain
    • Connection between PARP-1 enzymatic activity and repression incompletely defined
  6. 2013 Medium

    Defined a feed-forward loop in which ABL1 kinase activation by alpha-synuclein impedes its own autophagic clearance, identifying a druggable node (Nilotinib).

    Evidence Lentiviral SNCA/Abl expression, Nilotinib treatment, subcellular fractionation in transgenic and lentiviral mouse models

    PMID:23787811

    Open questions at the time
    • Direct phosphorylation substrate relationships not fully mapped
    • Single lab
  7. 2014 High

    Showed that pathogenic missense mutations divergently alter fibril formation kinetics, dissociating aggregation rate from cellular toxicity potential.

    Evidence Recombinant aggregation assays (fluorometry, EM, AFM) plus cell-based seeding and viability for H50Q and G51D

    PMID:24984882

    Open questions at the time
    • Did not resolve mutation-specific fibril architecture
    • Stress-condition toxicity mechanism not defined
  8. 2014 Medium

    Linked autophagy capacity to secretion route, demonstrating that ALP inhibition lowers intracellular aggregation but redirects oligomers to exosomal/RAB11A and shedding-based secretion that worsens microenvironmental toxicity.

    Evidence Cell and transgenic mouse models, bafilomycin A1, exosome fractionation, toxicity assays

    PMID:25484190

    Open questions at the time
    • Molecular machinery selecting exosome versus shedding routes not defined
    • Single lab
  9. 2014 High

    Established intron 1 DNA methylation as a direct, editable lever on SNCA expression with phenotypic consequences in patient neurons.

    Evidence dCas9-DNMT3A targeted methylation in iPSC-derived dopaminergic neurons from an SNCA-triplication patient, with ROS and viability rescue

    PMID:30266652

    Open questions at the time
    • Endogenous regulators establishing this methylation unknown
    • Single patient line
  10. 2015 Medium

    Placed GBA loss-of-function upstream of SNCA accumulation through a PPP2A-inactivation, autophagy-suppressing mechanism, mechanistically connecting a major genetic risk gene to clearance failure.

    Evidence GBA siRNA knockdown with PPP2A-activating rescue in cells, neurons, and rat striatum

    PMID:26378614

    Open questions at the time
    • Precise step of autophagy regulated by PPP2A not pinpointed
    • Single lab
  11. 2017 Medium

    Defined a BAG3–HSP70–p62 chaperone module that channels alpha-synuclein into macroautophagy, identifying the adaptor machinery for its degradation.

    Evidence Co-IP, colocalization, BAG3 gain/loss with ATG5-knockdown epistasis in PC12 cells and A53T transgenic mice

    PMID:28941726

    Open questions at the time
    • Reciprocal validation of each interaction limited
    • Selectivity for alpha-synuclein over other substrates unclear
  12. 2020 Medium

    Demonstrated activity-dependent synaptic vesicle association in a physiological knock-in model, grounding the protein's normal presynaptic role.

    Evidence Snca-GFP knock-in mouse with live terminal imaging during depolarization

    PMID:32788297

    Open questions at the time
    • Functional consequence of dispersal for vesicle cycling not defined
    • Did not identify vesicle-binding partners
  13. 2021 High

    Identified H3K4me3 enrichment at the SNCA promoter in PD substantia nigra and showed locus-specific demethylation lowers expression, adding a histone-mark regulatory layer.

    Evidence ChIP on post-mortem brain plus dCas9-SunTag-JARID1A editing in SH-SY5Y and iPSC-derived neurons

    PMID:33428332

    Open questions at the time
    • Writers/erasers maintaining the mark endogenously not defined
    • Single lab
  14. 2021 Medium

    Established miR-30b as a direct 3'-UTR-binding repressor of SNCA with protective phenotypic effects, adding post-transcriptional control.

    Evidence Luciferase 3'-UTR reporter, miR-30b mimics/inhibitors, viability and apoptosis assays in SH-SY5Y under MPP+

    PMID:32154657

    Open questions at the time
    • Single reporter method for binding without endogenous target validation
    • In vivo relevance untested
  15. 2021 Medium

    Showed that SNCA mRNA is depleted specifically in neurons bearing compact inclusions, linking inclusion formation to transcript loss.

    Evidence RNAscope with immunofluorescence in post-mortem LBD brain plus single-nucleus RNA-seq

    PMID:37996943

    Open questions at the time
    • Causal direction (depletion driving versus following inclusions) unresolved
    • Correlative tissue analysis
  16. 2021 Medium

    Characterized the A30G mutation as a local disorder perturbation that promotes fibrillization, expanding the genotype–aggregation map.

    Evidence NMR and biophysical characterization with fibril assay, plus exome/haplotype analysis of patient

    PMID:33617693

    Open questions at the time
    • Cellular toxicity not directly assessed
    • Single-family report
  17. 2022 Medium

    Identified cathepsin D as the lysosomal protease executing SNCA degradation and showed enzyme delivery reduces insoluble protein, defining a terminal clearance step.

    Evidence Recombinant pro-CTSD uptake/maturation in iPSC-derived A53T neurons and ctsd-knockout mouse brain

    PMID:35287553

    Open questions at the time
    • Cleavage sites and fragment fate not mapped
    • Single lab
  18. 2023 High

    Resolved disease-specific atomic folds of patient-derived filaments, including a novel juvenile-onset fold not reproducible in vitro, establishing structural strain diversity and a cofactor requirement.

    Evidence Cryo-EM of sarkosyl-insoluble filaments from JOS, with recombinant in vitro assembly and mass spectrometry

    PMID:36847833

    Open questions at the time
    • Identity of the non-proteinaceous cofactor unknown
    • Mechanism generating strain-specific folds in vivo undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How activity-dependent synaptic function, multilayered dosage control, and clearance failure converge to nucleate the distinct cofactor-dependent fibril strains that define each synucleinopathy remains unresolved.
  • No mechanism linking native synaptic-vesicle biology to strain-specific aggregation
  • Identity of cofactors templating disease-specific folds unknown
  • How clearance impairment selects secretion/spreading routes in vivo undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008289 lipid binding 2
Localization
GO:0031410 cytoplasmic vesicle 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-9612973 Autophagy 5 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ABL1APPBAG3CTSDHSPA8PARP1SQSTM1

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 NACP (alpha-synuclein) is a natively unfolded protein: it has a larger Stokes radius and slower sedimentation than globular proteins of similar molecular weight, lacks significant secondary structure (by CD and FTIR), lacks a hydrophobic core, and its conformation is unchanged by boiling, pH, salt, or chemical denaturants, indicating it exists as a mixture of rapidly equilibrating extended conformers. Analytical ultracentrifugation, gel filtration, circular dichroism (CD), Fourier-transform infrared spectroscopy (FTIR), UV spectroscopy Biochemistry High 8901511
1995 NACP (alpha-synuclein) binds to amyloid beta (Aβ) peptides through its NAC domain (specifically requiring the hydrophobic region of Aβ, residues 25–35), and at a 1:125 molar ratio promotes Aβ aggregation in aqueous solution; a deletion mutant lacking the NAC domain does not bind Aβ. Nitrocellulose filter-binding assay with recombinant NACP produced in E. coli, deletion mutagenesis (NACP-delta lacking NAC domain), peptide competition assay, aggregation assay Proceedings of the National Academy of Sciences of the United States of America High 7568089
1997 NACP (alpha-synuclein) exhibits an extended, largely random-coil structure in solution: it migrates anomalously on gel-filtration with an apparent molecular mass of ~70 kDa (true MW ~14 kDa), is extremely sensitive to limited proteolysis, and CD spectra confirm predominantly unfolded conformation. FPLC gel-filtration chromatography, chemical cross-linking, limited proteolysis, circular dichroism Molecules and cells Medium 9085269
2001 NACP-Rep1, a polymorphic microsatellite ~10 kb upstream of SNCA, acts as a negative modulator of SNCA transcription, with different alleles producing up to 3-fold variation in luciferase reporter expression in SH-SY5Y neuroblastoma cells; an 880 bp fragment containing NACP-Rep1 is necessary for normal expression and two flanking domains interact to enhance expression. Luciferase reporter assay with deletion constructs spanning 10.7 kb upstream of SNCA in 293T and SH-SY5Y cells, allele-specific reporter constructs Human molecular genetics Medium 11751692
2005 PARP-1 (poly-ADP-ribose polymerase-1) binds specifically to the NACP-Rep1 microsatellite upstream of SNCA and down-regulates SNCA transcription in a Rep1-dependent manner; inhibition of PARP-1 catalytic activity increases endogenous SNCA mRNA levels in SH-SY5Y cells. Pulldown of Rep1-binding proteins followed by mass spectrometry identification; EMSA (electrophoresis mobility shift assay); chromatin immunoprecipitation (ChIP); luciferase reporter assay; pharmacological inhibition of PARP-1 with 3-aminobenzamide; qRT-PCR of endogenous SNCA mRNA American journal of human genetics High 15672325
2014 DNA methylation at SNCA intron 1 regulates SNCA transcription; targeted methylation editing using dCas9-DNMT3A at intron 1 in iPSC-derived dopaminergic neurons from a patient with SNCA triplication reduced SNCA mRNA and protein levels and rescued disease-related phenotypes (mitochondrial ROS production and reduced cellular viability). CRISPR-dCas9 fused to DNMT3A catalytic domain (lentiviral delivery); hiPSC-derived dopaminergic neurons; qRT-PCR; Western blot; mitochondrial ROS assay; cell viability assay Molecular therapy High 30266652
2021 H3K4me3 is significantly elevated at the SNCA promoter in substantia nigra neurons of PD patients; CRISPR/dCas9-SunTag-JARID1A-mediated locus-specific demethylation of H3K4me3 at the SNCA promoter reduced alpha-synuclein mRNA and protein in SH-SY5Y cells and iPSC-derived dopaminergic neurons from idiopathic PD patients. ChIP-seq/ChIP analysis of post-mortem brain; CRISPR/dCas9-SunTag-JARID1A system; qRT-PCR; Western blot; iPSC-derived dopaminergic neurons; NeuN-sorted neuronal nuclei EMBO molecular medicine High 33428332
2014 The H50Q SNCA mutation increases the rate of alpha-synuclein aggregation into amyloid fibrils in vitro, whereas the G51D mutation has the opposite effect (decreased aggregation rate), yet both mutant proteins can be seeded to form intracellular aggregates by exogenous amyloidogenic seeds and promote cellular toxicity under stress conditions. Recombinant protein aggregation assay (bis-styrylbenzene fluorometry), sedimentation analysis, electron microscopy, atomic force microscopy, cell-based aggregation seeding assay, cell viability assay Journal of neurochemistry High 24984882
2023 Cryo-EM structures of alpha-synuclein filaments extracted from a case of juvenile-onset synucleinopathy (caused by a 21-nucleotide SNCA duplication) reveal a novel fold (residues 36–100 forming a compact core) that differs from Lewy body disease and MSA folds; the fold shares partial structural similarity with MSA protofilament substructures and contains a non-proteinaceous cofactor binding site; in vitro assembly of recombinant wild-type and insertion-mutant alpha-synuclein did not reproduce the JOS fold. Electron cryo-microscopy (cryo-EM) structure determination of patient-derived sarkosyl-insoluble filaments; in vitro assembly of recombinant proteins; mass spectrometry Acta neuropathologica High 36847833
2014 Autophagy-lysosomal pathway (ALP) inhibition by bafilomycin A1 reduces intracellular SNCA aggregation but increases secretion of smaller oligomeric SNCA species predominantly via exosomes and RAB11A-associated pathways, whereas high-aggregated SNCA is secreted by membrane shedding; the secreted oligomers exacerbate microenvironmental toxicity. Cell culture model of SNCA aggregation; SNCA transgenic mice; pharmacological ALP inhibition (bafilomycin A1); immunoprecipitation; ELISA; live-cell imaging; exosome isolation; inflammation and cell-damage assays Autophagy Medium 25484190
2015 Loss of GBA (glucocerebrosidase) function increases SNCA levels by inhibiting autophagy via PPP2A (protein phosphatase 2A) inactivation through Tyr307 phosphorylation; activation of PPP2A with C2-ceramide or rapamycin reverses GBA knockdown-induced SNCA accumulation. siRNA knockdown of GBA in SK-N-SH cells and primary rat cortical neurons; pharmacological inhibition; Western blot; immunohistochemistry; flow cytometry; rat striatum in vivo model Autophagy Medium 26378614
2017 BAG3 interacts with HSP70 and sequestosome 1 (SQSTM1/p62) and co-localizes with these proteins and LC3 puncta in TH-positive neurons; BAG3 overexpression enhances autophagic degradation of SNCA, and this effect is prevented by ATG5 knockdown, placing BAG3 upstream of macroautophagy in SNCA clearance. Immunoprecipitation; immunostaining; Western blot; BAG3 overexpression and knockdown in PC12 cells; SNCAA53T transgenic mice; ATG5 siRNA knockdown Neurobiology of aging Medium 28941726
2013 ABL1 tyrosine kinase is activated by SNCA expression (via phosphorylation) and in turn increases SNCA levels; inhibition of ABL1 with Nilotinib facilitates autophagic clearance of SNCA, shifting SNCA from autophagic vacuoles to lysosomes in transgenic and lentiviral mouse models. Lentiviral SNCA expression in mouse substantia nigra; lentiviral Abl overexpression; Nilotinib pharmacological treatment; subcellular fractionation; Western blot; transgenic mouse model Autophagy Medium 23787811
2022 CTSD (cathepsin D) is a lysosomal protease critical for SNCA degradation; recombinant human pro-CTSD (rHsCTSD) is endocytosed by neuronal cells, trafficked to lysosomes, and matured into an active enzyme that reduces insoluble SNCA in iPSC-derived dopaminergic neurons from PD patients with A53T SNCA mutation and in ctsd-deficient mouse brain. Recombinant protein treatment; immunofluorescence; Western blot; iPSC-derived dopaminergic neurons; ctsd-knockout mice; lysosomal activity assays; structured illumination microscopy Autophagy Medium 35287553
2020 In SNCA knock-in mice expressing aSyn-GFP under native regulatory elements, aSyn-GFP disperses from synaptic vesicles upon membrane depolarization, establishing that alpha-synuclein dynamically associates with synaptic vesicles and releases upon neuronal activity. Snca-GFP knock-in mouse; live imaging of synaptic terminals; membrane depolarization; confocal microscopy; intracerebral injection of preformed fibrils eNeuro Medium 32788297
2021 miR-30b directly binds to the 3'-UTR of SNCA mRNA and suppresses SNCA protein expression in SH-SY5Y cells, as demonstrated by luciferase reporter assay; miR-30b overexpression reduces SNCA protein levels and attenuates MPP+-induced apoptosis. Luciferase 3'-UTR reporter assay; miR-30b mimics/inhibitors transfection; Western blot; cell viability (CCK assay); apoptosis markers Brain and behavior Medium 32154657
2021 SNCA mRNA transcript levels are significantly reduced in neurons containing compact alpha-synuclein inclusions (but not in neurons with punctate or no alpha-synuclein staining) in the substantia nigra and amygdala of LBD patients, predominantly in the cytoplasmic compartment, suggesting progressive depletion of SNCA transcription or mRNA as inclusions form. RNAscope in situ hybridization combined with immunofluorescence for disease-associated alpha-synuclein in post-mortem LBD brain; single-nucleus RNA sequencing of non-diseased frontal cortex Acta neuropathologica communications Medium 37996943
2021 A novel SNCA A30G mutation causes a local perturbation of the intrinsically disordered structure of alpha-synuclein, slightly perturbs membrane binding, and promotes fibril formation in vitro. Biophysical characterization of recombinant A30G alpha-synuclein by NMR and other methods; fibril formation assay; whole exome sequencing and haplotype analysis Movement disorders Medium 33617693
1997 NACP (alpha-synuclein) is loosely associated with the plasma membrane, endomembrane system, and occasionally the membrane of secretory alpha-granules in platelets, as determined by immunogold electron microscopy. Immunogold electron microscopy of human platelets; immunoblotting; phorbol ester-induced megakaryocytic differentiation of K562 cells Biochemical and biophysical research communications Medium 9299413

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded. Biochemistry 1297 8901511
2010 Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update. Human mutation 402 20506312
1998 Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders. The American journal of pathology 367 9466562
1997 NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson's disease. Neuroscience letters 283 9547168
2007 Genetic variability in the SNCA gene influences alpha-synuclein levels in the blood and brain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 208 18162487
2001 Effect of allelic variation at the NACP-Rep1 repeat upstream of the alpha-synuclein gene (SNCA) on transcription in a cell culture luciferase reporter system. Human molecular genetics 204 11751692
2014 Autophagy modulates SNCA/α-synuclein release, thereby generating a hostile microenvironment. Autophagy 186 25484190
1999 Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. Brain research 179 10528110
2019 Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA). Autophagy 177 30983487
1995 NACP, the precursor protein of the non-amyloid beta/A4 protein (A beta) component of Alzheimer disease amyloid, binds A beta and stimulates A beta aggregation. Proceedings of the National Academy of Sciences of the United States of America 177 7568089
2014 APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease. JAMA neurology 171 25178429
2015 Autosomal dominant Parkinson's disease caused by SNCA duplications. Parkinsonism & related disorders 167 26350119
2018 Genotype-phenotype relations for the Parkinson's disease genes SNCA, LRRK2, VPS35: MDSGene systematic review. Movement disorders : official journal of the Movement Disorder Society 155 30357936
2018 Downregulation of SNCA Expression by Targeted Editing of DNA Methylation: A Potential Strategy for Precision Therapy in PD. Molecular therapy : the journal of the American Society of Gene Therapy 150 30266652
2010 SNCA variant associated with Parkinson disease and plasma alpha-synuclein level. Archives of neurology 148 21060011
1996 Altered presynaptic protein NACP is associated with plaque formation and neurodegeneration in Alzheimer's disease. The American journal of pathology 147 8546207
2016 The Parkinson Disease gene SNCA: Evolutionary and structural insights with pathological implication. Scientific reports 124 27080380
2018 The lysosomal membrane protein LAMP2A promotes autophagic flux and prevents SNCA-induced Parkinson disease-like symptoms in the Drosophila brain. Autophagy 117 29989488
2008 Patients homozygous and heterozygous for SNCA duplication in a family with parkinsonism and dementia. Archives of neurology 109 18413475
2014 Divergent effects of the H50Q and G51D SNCA mutations on the aggregation of α-synuclein. Journal of neurochemistry 108 24984882
2015 GBA deficiency promotes SNCA/α-synuclein accumulation through autophagic inhibition by inactivated PPP2A. Autophagy 107 26378614
1997 NACP, a synaptic protein involved in Alzheimer's disease, is differentially regulated during megakaryocyte differentiation. Biochemical and biophysical research communications 101 9299413
2015 Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation. Molecular neurodegeneration 99 26306801
2021 A Novel SNCA A30G Mutation Causes Familial Parkinson's Disease. Movement disorders : official journal of the Movement Disorder Society 87 33617693
1995 The NACP/synuclein gene: chromosomal assignment and screening for alterations in Alzheimer disease. Genomics 85 7601450
2013 Hypomethylation of SNCA in blood of patients with sporadic Parkinson's disease. Journal of the neurological sciences 83 24326201
2011 Independent and joint effects of the MAPT and SNCA genes in Parkinson disease. Annals of neurology 78 21391235
2005 Regulation of alpha-synuclein expression by poly (ADP ribose) polymerase-1 (PARP-1) binding to the NACP-Rep1 polymorphic site upstream of the SNCA gene. American journal of human genetics 78 15672325
2021 Targeted attenuation of elevated histone marks at SNCA alleviates α-synuclein in Parkinson's disease. EMBO molecular medicine 75 33428332
2023 New SNCA mutation and structures of α-synuclein filaments from juvenile-onset synucleinopathy. Acta neuropathologica 70 36847833
2000 Properties of NACP/alpha-synuclein and its role in Alzheimer's disease. Biochimica et biophysica acta 70 10899435
2021 Piperine promotes autophagy flux by P2RX4 activation in SNCA/α-synuclein-induced Parkinson disease model. Autophagy 68 34092198
2022 Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models. Autophagy 67 35287553
2018 Engineering synucleinopathy-resistant human dopaminergic neurons by CRISPR-mediated deletion of the SNCA gene. The European journal of neuroscience 67 30472757
2014 Genetic variants and animal models in SNCA and Parkinson disease. Ageing research reviews 66 24768741
2000 NACP/alpha-synuclein and tau constitute two distinctive subsets of filaments in the same neuronal inclusions in brains from a family of parkinsonism and dementia with Lewy bodies: double-immunolabeling fluorescence and electron microscopic studies. Acta neuropathologica 65 10963357
2016 Parkinson's disease: SNCA-, PARK2-, and LRRK2- targeting microRNAs elevated in cingulate gyrus. Parkinsonism & related disorders 63 27717584
2014 Link between the SNCA gene and parkinsonism. Neurobiology of aging 61 25554495
2021 Midbrain organoids with an SNCA gene triplication model key features of synucleinopathy. Brain communications 60 34632384
2017 Deregulation of α-synuclein in Parkinson's disease: Insight from epigenetic structure and transcriptional regulation of SNCA. Progress in neurobiology 59 28445713
2018 A comprehensive analysis of SNCA-related genetic risk in sporadic parkinson disease. Annals of neurology 53 30146727
2004 Australian data and meta-analysis lend support for alpha-synuclein (NACP-Rep1) as a risk factor for Parkinson's disease. Neuroscience letters 53 15670652
2017 A role of BAG3 in regulating SNCA/α-synuclein clearance via selective macroautophagy. Neurobiology of aging 52 28941726
1997 Evidence that the precursor protein of non-A beta component of Alzheimer's disease amyloid (NACP) has an extended structure primarily composed of random-coil. Molecules and cells 52 9085269
2017 Genetic Variants in SNCA and the Risk of Sporadic Parkinson's Disease and Clinical Outcomes: A Review. Parkinson's disease 49 28781905
2013 Tyrosine kinase inhibition facilitates autophagic SNCA/α-synuclein clearance. Autophagy 49 23787811
2018 SNCA Is a Functionally Low-Expressed Gene in Lung Adenocarcinoma. Genes 48 29300342
2016 DNA methylation changes at SNCA intron 1 in patients with dementia with Lewy bodies. Psychiatry and clinical neurosciences 48 27685250
2015 Detection of SNCA and FBN1 methylation in the stool as a biomarker for colorectal cancer. Disease markers 48 25802477
2012 Analysis of LRRK2, SNCA, Parkin, PINK1, and DJ-1 in Zambian patients with Parkinson's disease. Parkinsonism & related disorders 48 22445250
2018 LncRNA-UCA1 promotes PD development by upregulating SNCA. European review for medical and pharmacological sciences 47 30536337
2022 Parkinson's Disease Derived Exosomes Aggravate Neuropathology in SNCA*A53T Mice. Annals of neurology 46 35596947
2015 Clinical and imaging findings in Parkinson disease associated with the A53E SNCA mutation. Neurology. Genetics 45 27066564
2022 CRISPR-Cas9 Gene Editing Protects from the A53T-SNCA Overexpression-Induced Pathology of Parkinson's Disease In Vivo. The CRISPR journal 42 35191750
2007 Screening for SNCA and LRRK2 mutations in Greek sporadic and autosomal dominant Parkinson's disease: identification of two novel LRRK2 variants. European journal of neurology 41 17222106
2020 Evaluating the Role of SNCA, LRRK2, and GBA in Chinese Patients With Early-Onset Parkinson's Disease. Movement disorders : official journal of the Movement Disorder Society 39 32677286
2011 SNCA and MAPT genes: Independent and joint effects in Parkinson disease in the Italian population. Parkinsonism & related disorders 39 22104010
2021 The Impact of SNCA Variations and Its Product Alpha-Synuclein on Non-Motor Features of Parkinson's Disease. Life (Basel, Switzerland) 37 34440548
2014 Pyrosequencing analysis of SNCA methylation levels in leukocytes from Parkinson's disease patients. Neuroscience letters 37 24721670
2021 HIV-1 Vpr protein impairs lysosome clearance causing SNCA/alpha-synuclein accumulation in neurons. Autophagy 35 33890542
2019 Investigation of somatic CNVs in brains of synucleinopathy cases using targeted SNCA analysis and single cell sequencing. Acta neuropathologica communications 35 31870437
2016 Elevated mRNA Expression and Low Methylation of SNCA in Japanese Alzheimer's Disease Subjects. Journal of Alzheimer's disease : JAD 35 27567856
2010 SNCA, MAPT, and GSK3B in Parkinson disease: a gene-gene interaction study. European journal of neurology 35 21159074
2000 Accumulation of NACP/alpha-synuclein in lewy body disease and multiple system atrophy. Journal of neurology, neurosurgery, and psychiatry 33 10766891
2011 SNCA locus duplication carriers: from genetics to Parkinson disease phenotypes. Human mutation 32 21412942
2015 Alpha-synuclein (SNCA) polymorphisms and susceptibility to Parkinson's disease: a meta-analysis. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 31 25656566
2020 miR-30b protects nigrostriatal dopaminergic neurons from MPP(+)-induced neurotoxicity via SNCA. Brain and behavior 30 32154657
2017 Variants in SNCA Gene Are Associated with Parkinson's Disease Risk and Cognitive Symptoms in a Brazilian Sample. Frontiers in aging neuroscience 30 28676755
2016 Common variant rs356182 near SNCA defines a Parkinson's disease endophenotype. Annals of clinical and translational neurology 30 28078311
2011 Genetic variability in SNCA and Parkinson's disease. Neurogenetics 28 21800132
2015 Variants in the SNCA gene associate with motor progression while variants in the MAPT gene associate with the severity of Parkinson's disease. Parkinsonism & related disorders 27 26776090
2012 SNCA polymorphisms, smoking, and sporadic Parkinson's disease in Japanese. Parkinsonism & related disorders 27 22425546
1998 Changes in presynaptic protein NACP/alpha-synuclein in an ischemic gerbil hippocampus. Brain research 27 9555070
2021 α-Synuclein antisense transcript SNCA-AS1 regulates synapses- and aging-related genes suggesting its implication in Parkinson's disease. Aging cell 26 34799977
2022 Autophagy mediates the clearance of oligodendroglial SNCA/alpha-synuclein and TPPP/p25A in multiple system atrophy models. Autophagy 25 35000546
2019 Multiplication of the SNCA locus exacerbates neuronal nuclear aging. Human molecular genetics 25 30304516
2018 SNCA, a novel biomarker for Group 4 medulloblastomas, can inhibit tumor invasion and induce apoptosis. Cancer science 25 29369502
2020 Snca-GFP Knock-In Mice Reflect Patterns of Endogenous Expression and Pathological Seeding. eNeuro 21 32788297
2019 Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K-SNCA mutation carriers. Parkinsonism & related disorders 21 31178336
2011 Do interactions between SNCA, MAPT, and LRRK2 genes contribute to Parkinson's disease susceptibility? Parkinsonism & related disorders 21 21816655
2023 The G51D SNCA mutation generates a slowly progressive α-synuclein strain in early-onset Parkinson's disease. Acta neuropathologica communications 20 37138318
2021 Cell-Type Specific Changes in DNA Methylation of SNCA Intron 1 in Synucleinopathy Brains. Frontiers in neuroscience 20 33994928
2019 SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson's Disease. Movement disorders : official journal of the Movement Disorder Society 20 31234232
2017 Blood RNA biomarkers in prodromal PARK4 and rapid eye movement sleep behavior disorder show role of complexin 1 loss for risk of Parkinson's disease. Disease models & mechanisms 20 28108469
2021 Investigating the relationship between the SNCA gene and cognitive abilities in idiopathic Parkinson's disease using machine learning. Scientific reports 19 33649398
2015 SNCA Gene, but Not MAPT, Influences Onset Age of Parkinson's Disease in Chinese and Australians. BioMed research international 19 25960998
2023 Neuronal SNCA transcription during Lewy body formation. Acta neuropathologica communications 18 37996943
2022 Modeling native and seeded Synuclein aggregation and related cellular dysfunctions in dopaminergic neurons derived by a new set of isogenic iPSC lines with SNCA multiplications. Cell death & disease 18 36261424
2021 Genetic Analysis and Literature Review of SNCA Variants in Parkinson's Disease. Frontiers in aging neuroscience 18 34456707
2020 SNCA Hypomethylation in Rapid Eye Movement Sleep Behavior Disorder Is a Potential Biomarker for Parkinson's Disease. Journal of Parkinson's disease 18 32444558
2022 Linking the phenotype of SNCA Triplication with PET-MRI imaging pattern and alpha-synuclein CSF seeding. NPJ Parkinson's disease 17 36109514
2019 SNCA Rep1 promoter variability influences cognition in Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society 17 31234238
2018 Association of SNCA variants with α-synuclein of gastric and colonic mucosa in Parkinson's disease. Parkinsonism & related disorders 17 30424941
2017 Structural variants in SNCA gene and the implication to synucleinopathies. Current opinion in genetics & development 17 28319736
2024 Novel Therapeutic Horizons: SNCA Targeting in Parkinson's Disease. Biomolecules 16 39199337
2021 Prodromal sensory neuropathy in Pink1-/- SNCAA53T double mutant Parkinson mice. Neuropathology and applied neurobiology 16 33974284
2020 A population scale analysis of rare SNCA variation in the UK Biobank. Neurobiology of disease 16 33307186
2020 Metal Exposure and SNCA rs356219 Polymorphism Associated With Parkinson Disease and Parkinsonism. Frontiers in neurology 16 33362685
2019 SerThr-PhosphoProteome of Brain from Aged PINK1-KO+A53T-SNCA Mice Reveals pT1928-MAP1B and pS3781-ANK2 Deficits, as Hub between Autophagy and Synapse Changes. International journal of molecular sciences 16 31277379
2016 Mutation analysis of the PARKIN, PINK1, DJ1, and SNCA genes in Turkish early-onset Parkinson's patients and genotype-phenotype correlations. Clinical neurology and neurosurgery 16 27455133

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