Phosphorylated α-Synuclein-Copper Complex Formation in the Pathogenesis of Parkinson’s Disease

Figure 2

Cell alterations involved in the aggregation process of -synuclein. Damaged or unrequired proteins are regulated by both the proteasomal and lysosomal degradation pathways. UPS disruption leads to activation of the ALS and vice versa, as a compensation mechanism. Both mechanisms are affected in PD, which results in protein accumulation including α-synuclein and ubiquitin-bound proteins. Accumulation of unfolded or misfolded proteins into the endoplasmic reticulum activates the unfolded protein response. Mitochondrial dysfunction and oxidative stress are also interrelated and linked to the pathogenesis of PD. All these alterations are associated with the phosphorylation process of α-synuclein and increase α-synuclein oligomerization, leading to Lewy body formation and subsequent apoptotic cell death.