alpha-Syn (alpha-synuclein) is a small soluble acidic protein that is extensively expressed in the nervous system. Genetic, clinical and experimental studies demonstrate that alpha-syn is strongly implicated in the pathogenesis of PD (Parkinson's disease). However, the pathogenic mechanism remains elusive. In the present chapter, we first describe the normal expression and potential physiological functions of alpha-syn. Then, we introduce recent research progress related to the pathogenic role of alpha-syn in PD, with special emphasis on how alpha-syn oligomers cause the preferential degeneration of dopanninergic neurons in the substantia nigra and the spreading of alpha-syn pathology in the brain of PD patients.