ArticleParkinsonism & related disorders2014
Does α-synuclein have a dual and opposing effect in preclinical vs. clinical Parkinson's disease?
Article in Parkinsonism & related disorders, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Genome-Wide Association Studies of Cognitive and Motor Progression in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021Pooled it
- A personalised and comprehensive approach is required to suppress or replenish SNCA for Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- Nonintuitive Immunogenicity and Plasticity of Alpha-Synuclein Conformers: A Paradigm for Smart Delivery of Neuro-Immunotherapeutics.Pharmaceutics · 2024Review
- Neurocognitive Impairment and Social Cognition in Parkinson's Disease Patients.Neurology international · 2024Review
- Unraveling the Complex Interplay between Alpha-Synuclein and Epigenetic Modification.International journal of molecular sciences · 2023Review
- α-Synuclein in synaptic function and dysfunction.Trends in neurosciences · 2023Review
- Synaptic vesicle binding of α-synuclein is modulated by β- and γ-synucleins.Cell reports · 2022Article
- The Impact ofLife (Basel, Switzerland) · 2021Review
- Alpha-synuclein research: defining strategic moves in the battle against Parkinson's disease.NPJ Parkinson's disease · 2021Review
- A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson's disease.NPJ Parkinson's disease · 2021Review
- Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson's disease.Nature genetics · 2021Article
- "Janus-Faced" α-Synuclein: Role in Parkinson's Disease.Frontiers in cell and developmental biology · 2021Review
- Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort.Frontiers in neurology · 2021Article
- The Length ofFrontiers in neurology · 2018Article
- Silencing Alpha Synuclein in Mature Nigral Neurons Results in Rapid Neuroinflammation and Subsequent Toxicity.Frontiers in molecular neuroscience · 2018Article
- Inventory of real world data sources in Parkinson's disease.BMC neurology · 2017Review
- Variants in SNCA Gene Are Associated with Parkinson's Disease Risk and Cognitive Symptoms in a Brazilian Sample.Frontiers in aging neuroscience · 2017Article
- Genetic Variants in SNCA and the Risk of Sporadic Parkinson's Disease and Clinical Outcomes: A Review.Parkinson's disease · 2017Review
- Common variant rs356182 near SNCA defines a Parkinson's disease endophenotype.Annals of clinical and translational neurology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
α-Synuclein gene (SNCA) multiplications cause familial parkinsonism and allele-length polymorphisms within the SNCA dinucleotide repeat REP1 increase the risk for developing Parkinson's disease (PD). Since SNCA multiplications increase SNCA expression, and REP1 genotypes that increase the risk of developing PD show increased SNCA expression in cell-culture systems, animal models, and human blood and brain, PD therapies seek to reduce SNCA expression. We conducted an observational study of 1098 PD cases to test the hypothesis that REP1 genotypes correlated with reduced SNCA expression are associated with better motor and cognitive outcomes. We evaluated the association of REP1 genotypes with survival free of Hoehn and Yahr stages 4 or 5 (motor outcome) and of Modified Telephone Interview for Cognitive Status score ≤27 or Alzheimer's Disease Dementia Screening Interview score ≥2 (cognitive outcome). Median disease duration at baseline was 3.3 years and median lag time from baseline to follow-up was 7.8 years. Paradoxically, REP1 genotypes associated with increased risk of developing PD and increased SNCA expression were associated with better motor (HR = 0.87, p = 0.046, covariate-adjusted age-scale analysis; HR = 0.85, p = 0.020, covariate-adjusted time-scale analysis) and cognitive outcomes (HR = 0.90, p = 0.12, covariate-adjusted age-scale analysis; HR = 0.85, p = 0.023, covariate-adjusted time-scale analysis). Our findings raise the possibility that SNCA has a dual, opposing, and time-dependent role. This may have implications for the development of therapies that target SNCA expression.
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What OpenQuestion holds
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.