Our study provides strong support for the susceptibility role of SNCArs356219 in sporadic PD in a Han Chinese population from mainland China and the meta-analysis also revealed a similar finding in the Asian population.
By comparing results of a GWAS performed on individuals of European ancestry, we identified PARK16, SNCA and LRRK2 as shared risk loci for PD and BST1 and MAPT as loci showing population differences.
However, the precise variants within SNCA gene that contribute to the sporadic forms of Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and other synucleinopathies and their molecular mechanisms of action remain elusive.
As a model for PD, we generated human α-syn bacterial artificial chromosome transgenic mice (BAC tg mice) harboring the entire human α-syn gene and its gene expression regulatory regions.
The discovery of SNCA mutations pathogenic for autosomal-dominant Lewy body Parkinson's disease (PD) in 1997 heralded a revolution in understanding the molecular and genetic basis of PD.
Missense point mutations, duplication and triplication in the alpha-synuclein (alphaSYN) gene have been identified in familial Parkinson's disease (PD).
Two missense mutations of the alpha-synuclein (alpha-syn; A30P and A53T) have been described in several families with an autosomal dominant form of PD. alpha-Syn also constitutes one of the main components of Lewy bodies in sporadic cases of PD.
The prion-like activity and morphology of α-synuclein fibrils from CHCHD2 T61I brain tissue were similar to those of fibrils from SNCA duplication and sporadic PD brain tissues.
Mutations in three of these genes, PRKN, PINK1, and DJ1, are important in early onset, recessively inherited PD, while mutations in LRRK2 and SNCA result in autosomal-dominant PD.
These results suggest that widespread accumulation of HtrA2/Omi may occur in pathologic alpha-synuclein-containing inclusions in brains with PD, DLB, or MSA and that HtrA2/Omi may be associated with the pathogenesis of alpha-synucleinopathies.
Here we first provided evidence that RV treatment alleviated motor and cognitive deficits in the A53Tα-synuclein mouse model of PD in a dose-dependent manner.
Rare mutations in the alpha-synuclein and synphilin-1 genes have been implicated in the pathogenesis of PD; however, the normal function of these proteins is far from being completely elucidated.
The finding of a mutation in the alpha-synuclein gene in a rare autosomal dominant form of idiopathic Parkinson's disease (IPD), has prompted increased interest in identifying genes that account for the more common sporadic form.