[PDF] α-Synuclein Locus Triplication Causes Parkinson's Disease | Semantic Scholar (2024)

The objective of this study was to assess the frequency of SNCA multiplications among autosomal dominant hereditary Parkinson's disease (ADPD) patients.

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.

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.

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.

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.

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It is demonstrated that genetic variability in the α-synuclein gene is a risk factor for the development of PD and these genetic findings are analogous to the tau haplotype over-represented in progressive supranuclear palsy.

A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.

Examination of brains from patients with multiple system atrophy suggested that a reduction in the solubility of α‐synuclein may induce this protein to form filaments that aggregate into cytoplasmic inclusions, which contribute to the dysfunction or death of glial cells as well as neurons in neurodegenerative disorders with different phenotypes.

Data demonstrate a new locus for Lewy body parkinsonism and suggest that in some circ*mstances postural tremor can be an alternative phenotype of the samepathogenic mutation as Lewy Body Parkinsonism.