Pilot study: molecular risk factors for diagnosing sporadic Parkinson's disease based on gene expression in blood in MPTP-induced rhesus monkeys

Abstract

Clinical diagnosis of Parkinson’s disease (PD) is characterized by the classical features of tremor, bradykinesia and rigidity, which are present only when more than 70%-80% degeneration of dopaminergic (DA) neurons in the substantia nigra. The lack of means for early diagnosis of PD has elicited interest in searching for its risk factors, which, by now, are almost obtained at a single time point in PD process, and little developing risk factors, obtained from completely normal situation to the onset or even advanced stage of PD in individual person which could monitor the progress of PD, are present. Here we have detected some potential factors in the blood of MPTP induced PD monkeys along with the progress of the disease. All the PD monkeys showed mild PD symptoms since the 9^th week and gradually reached a classic and stable parkinsonism stage at the 18^th week. Our results have found that the expression of Parkin, USP30, MUL1, PINK1, and LRRK2 significantly increased at 1^st, 3^th, 3^th, 5^th, and 8^th week respectively and remained high till the end; The expression of UCHL1 and TRIM24 significantly increased at the 1^st and 18^th week, respectively, then gradually decreased and significantly lower than normal value; DJ-1 showed significantly decreased since the 12^th week, while SNCA showed no significantly changed excepted at the 5^th week. And, the terminal results of whole blood were highly consistent with those of in SN. These results support that these genes change may as biomarkers to monitor the progress of PD, and may facilitate the development of biomarkers for early diagnosis.