Focus on another PD protein: Alpha -Synuclein (a-syn)

The first genetic cause for PD was described in a large Italian family that inherited early-onset PD in an autosomal dominant fashion. Subsequently, missense mutations in the a-syn gene were also identified in Greek, German, and
Spanish families, with missense mutations localized to the N-terminal half of the protein. As opposed to missense mutations in LRRK2, pathogenic missense mutations
in the a-syn gene seem confined to only a handful of PD cases worldwide. Again in contrast with LRRK2, genetic variation in the a-syn promoter and other regions of the gene appears to modify susceptibility to PD. The identification of genomic multiplications that include a-syn and are causative for PD solidifies the importance of a-syn dosage in PD. The main strength that suggests a critical involvement
for a-syn in PDdoes not necessarily lie with human genetic studies; rather, a-syn represents the major protein component of the pathologic structures that define PD associated lesions in affected regions of the brain.