Genetic variants and animal models in SNCA and Parkinson disease

• This review focuses on genetic studies of the SNCA gene in PD.
• Point mutation and multiplication are the main types of mutation in the SNCA gene.
• Though the frequency of mutations is low, SNCA plays a central role in PD.
• Genetic modified animal models of PD relating to the SNCA gene were summarized.
• Genetic findings of SNCA can provide insights into pathogenesis and therapy of PD.

Parkinson disease (PD; MIM 168600) is the second most common progressive neurodegenerative disorder characterized by a variety of motor and non-motor features. To date, at least 20 loci and 15 disease-causing genes for parkinsonism have been identified. Among them, the α-synuclein (SNCA) gene was associated with PARK1/PARK4. Point mutations, duplications and triplications in the SNCA gene cause a rare dominant form of PD in familial and sporadic PD cases. The α-synuclein protein, a member of the synuclein family, is abundantly expressed in the brain. The protein is the major component of Lewy bodies and Lewy neurites in dopaminergic neurons in PD. Further understanding of its role in the pathogenesis of PD through various genetic techniques and animal models will likely provide new insights into our understanding, therapy and prevention of PD.