Elevated levels of α-Synuclein are found in patients with Parkinson's disease, and there seems to be a positive correlation between the amount of the α-Synuclein protein present in the patient and the severity of the disease. Phosphorylation of the amino acid Ser129 in the α-Synuclein protein has a profound effect on the severity of the disease. There seem to be correlation between the total α-Synuclein concentration (unphosphorylated) and the severity of the symptoms in Parkinson's disease patients. Healthy patients seem to have higher levels of unphosphorylated α-Synuclein than patients with Parkinson's disease. Moreover, the measurement of the changes in the ratio of concentrations of phosphorylated α-Synuclein to unphosphorylated α-Synuclein within a patient could be a potential marker of the disease progression. Antibodies that target α-Synuclein at phosphorylated Serine129 are widely used to study the molecular aspects of synucleinopathies Phosphorylation of Ser129 is associated with the aggregation of the protein and further damage to the nervous system. Furthermore, the aggregation of phosphorylated α-Synuclein can be enhanced if a presynaptic scaffold protein Sept4 is present in insufficient quantities. It is important to note that direct interaction of α-Synuclein with Sept4 protein inhibits the phosphorylation of Ser129. Note however that phosphorylation of Ser129 can be observed without synuclein aggregation in conditions of overexpression References Cell biology Cell signaling Phosphorus