Analysis of Brain Protein Stability Changes in Mouse Models of Normal Aging and a Synucleinopathy Reveals Age- and Disease-Related Differences

The lack of appropriate protein biomarkers makes the early detection of Parkinson’s disease (PD) challenging, and it thwarts efforts to develop drug therapies for this incurable disease. Thus, new approaches are needed for biomarker discovery and for better understanding the molecular basis of PD progression. Here, we utilize proteome-wide measurements of protein folding stability to characterize the progression of PD in a mouse model of the disease in which the human α-synuclein protein with an A53T mutation was overexpressed. Using the Stability of Proteins from Rates of Oxidation (SPROX) technique, the thermodynamic stabilities of proteins in brain tissue cell lysates from Huα-Syn(A53T) transgenic mice were profiled at three time points including at 1 month (n=9), at 6 months (n=7), and at the time (between 9 and 16 months) a mouse became Symptomatic (n=8).