α-Synuclein Locus Triplication Causes Parkinson's Disease

@article{Singleton2003SynucleinLT,
  title={$\alpha$-Synuclein Locus Triplication Causes Parkinson's Disease},
  author={Andrew B. Singleton and Matthew J Farrer and Janel O. Johnson and Amanda Singleton and Stephen Hague and Jennifer M. Kachergus and Mary Hulihan and Terhi Peuralinna and Amalia S Dutra and Robert Luke Nussbaum and Sarah J. Lincoln and Anthony Crawley and Melissa Hanson and Demetrius M. Maraganore and Charles H. Adler and Mark R. Cookson and Manfred D. Muenter and Melisa J. Baptista and David S. Miller and J. Blancato and John Hardy and Katrina Gwinn‐Hardy},
  journal={Science},
  year={2003},
  volume={302},
  pages={841 - 841}
}
Mutations in the α-synuclein gene ( SNCA ) in the Contursi kindred ([ 1 ][1]) implicated this gene in Parkinson's disease (PD). Subsequently, α-synuclein was identified as the major component of Lewy bodies, the pathological hallmark of PD, and of glial cell cytoplasmic inclusions ([ 2 ][2]). We 
Clinical heterogeneity of α‐synuclein gene duplication in Parkinson's disease
TLDR
The objective of this study was to assess the frequency of SNCA multiplications among autosomal dominant hereditary Parkinson's disease (ADPD) patients.
α-Synuclein in blood and brain from familial Parkinson disease with SNCA locus triplication
TLDR
Examination of brain tissue showed a doubling in the level of SNCA message, but at the protein level in brain, there was a greater effect on deposition of aggregated forms into insoluble fractions than on net expression of soluble α-synuclein.
Caught in the Act α-Synuclein Is the Culprit in Parkinson's Disease
TLDR
A recent report on the Iowan kindred provides new mechanistic insight into Parkinson's disease by showing that an elevation in wild-type α-synuclein protein is sufficient to develop the early-onset form of the disorder.
α-synuclein locus duplication as a cause of familial Parkinson's disease
TLDR
The clinical phenotype of SNCA duplication closely resembles idiopathic Parkinson's disease, which has a late age-of-onset, progresses slowly, and in which neither cognitive decline nor dementia are prominent, and suggest a direct relation between S NCA gene dosage and disease progression.
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TLDR
An overview of the implication of α-Syn pathology and its consequences on neuroinflammation in PD is provided.
Neurobiology of α-synuclein
TLDR
Recent data regarding the structure, the regulation at the transcriptional and posttranslational level, and the physiologic and aberrant functions of α-synuclein are reviewed, focusing in particular on the fibrilization potential and its link with defects in protein degradation.
The role of α-synuclein gene multiplications in early-onset Parkinson’s disease and dementia with Lewy bodies
TLDR
Mutational screening of the entire coding region of α-synuclein revealed only one silent mutation V3V (adenine9guanine) in one case and this phenomenon appears not to be a major cause in the pathogenesis of sporadic DLB and young onset PD in this European population.
α-Synuclein in Parkinson’s disease: causal or bystander?
TLDR
While rare SNCA gene mutations are causal for a minority of familial PD patients, in sporadic PD (where common S NCA polymorphisms are the most consistent genetic risk factor across populations worldwide, accounting for 95% of PD patients) α-syn pathology is an important feature.
Unaltered α-synuclein blood levels in juvenile Parkinsonism with a parkin exon 4 deletion
TLDR
This report tests whether there is also an increase of α-synuclein in autosomal recessive juvenile Parkinsonism (ARJP) and finds there is not and discusses this result in terms of the putative relationships between α- synuclein and parkin.
a-Synuclein and Parkinson's Disease
TLDR
The chapter discusses the SNCA multiplications; the pathogenic role of αSYN and its relation to cellular dysfunction and cell death; α-synuclein normal localization, regulation, and function;α- synuclein catabolism; numerous animal models for α SYN-related neurodegeneration; and SNCa genetics in sporadic disease.
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