Conversely, mutant alpha synuclein can cause a direct inhibitory effect on the 20S cores proteolytic capabilities and the downregulation of several subunits of the proteasome in the substantia nigra of PD patients (Chen et al., 2005; Emmanouilidou et al., 2010; Tanaka et al., 2001). This evidence concerns the gene SNCA and Parkinson disease.