The specific cascade of biological events underlying substantia nigra neurodegeneration in Parkinson's disease (PD) remains elusive. To gain new insights into PD pathogenesis, we conducted some proteomic investigations of nigral autopsy tissues from patients with PD and controls. Our approach highlighted a set of proteins differentially expressed in PD. A majority of them such as CNDP2 or nebulette were novel candidates potentially engaged in PD pathological process. Overall, observed alterations tended to confirm well accepted concepts surrounding PD pathogenesis but also pointed out the involvement of less conventional ones such as ER stress, cytoskeleton or extracellular matrix impairments. This project provides further insights into PD pathogenesis and may ultimately help to delineate new therapeutic targets and biomarkers for the treatment and diagnosis of PD.