alpha-Synuclein locus triplication causes Parkinson's disease.

By A. Singleton, M. Farrer, J. Johnson, A. Singleton, S. Hague, J. Kachergus, M. Hulihan, T. Peuralinna, A. Dutra, R. Nussbaum and 12 more. Science, 2003

2,110 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/0e1ce9304c80e213a64aa18511b0d799b6cacb68

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Citations in the corpus

• In vivo demonstration that α-synuclein oligomers are toxic (2011, background): “By using the weaker promoter, EF1α, the overexpression could be lowered considerably; however, it still exceeded the expression levels in cases of familial PD presenting a triplication in the α-syn gene (5) (Fig.”
• α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. (2011, unknown): “…by observations that inherited PD can arise following 3 missense mutations (5–7) as well as duplication and triplication in the α -syn gene (8, 9) and that aggregated α -syn is abundant in LB and LN also in sporadic PD. Recently, α -syn–positive LB and LN were detected in grafted neurons in…”
• Exosomal cell-to-cell transmission of alpha synuclein oligomers (2012, background): “Gene multiplication of the αsyn gene [2,3] and missense mutations [4-6] are linked to familial forms of PD.”
• Genome-Wide Association Study reveals genetic risk underlying Parkinson’s disease (2009, unknown): “Although mutations and copy number variants of SNCA are the cause of rare familial forms of PD10,13, association of common variants has been more controversial.”
• Exogenous α-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells (2009, background): “Misfolded -Syn could arise in a cell-autonomous manner via increased synthesis as seen in individuals with -Syn gene amplification (23) or by mutations that accelerate -Syn misfolding itself (e.”
• Prion-like spreading of pathological α-synuclein in brain (2013, background): “…E46K and A53T) in the -synuclein gene (Polymeropoulos et al., 1997; Kruger et al., 1998; Zarranz et al., 2004) and multiplications of the region (Singleton et al., 2003; Chartier-Harlin et al., 2004; Ibanez et al., 2004,) have been identified in familial forms of Parkinson’s disease and…”
• Comparison of kindreds with parkinsonism and α‐synuclein genomic multiplications (2004, background): “-Synuclein exon dosage was comparable to results from the Iowa family and consistent with SNCA genomic triplication (see Fig 1).(6) However, the region of triplication arose independently.”
• Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences (2012, unknown): “…a - synuclein gene and genomic duplications or triplications have been identified in patients with autosomal dominant parkinsonism (Polymeropoulos et al , 1997; Kruger et al , 1998; Singleton et al , 2003; Chartier-Harlin et al , 2004; Farrer et al , 2004; Ibanez et al , 2004; Zarranz et al , 2004).”
• Exogenous α-Synuclein Fibrils Induce Lewy Body Pathology Leading to Synaptic Dysfunction and Neuron Death (2011, unknown): “Interestingly, levels of α-syn increase with age (Chu and Kordower, 2007) and α-syn gene duplication and triplication can lead to PD (Singleton et al., 2003).”
• The Post-GWAS Era: From Association to Function. (2018, background): “The authors demonstrate that the SNCA risk haplotype is associated with increased SNCA brain expression, which has previously been associated with PD pathogenesis, since families with duplications or triplications of the SNCA locus (resulting in increased SNCA levels) exhibit Mendelian forms of PD.(”