Oxidative stress reflects an imbalance between the overproduction and incorporation of free radicals and the dynamic ability of a biosystem to detoxify reactive intermediates. Free radicals produced by oxidative stres...
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Oxidative stress reflects an imbalance between the overproduction and incorporation of free radicals and the dynamic ability of a biosystem to detoxify reactive intermediates. Free radicals produced by oxidative stress are one of the common features in several experimental models of diseases. Free radicals affect both the structure and function of neural cells,and contribute to a wide range of neurodegenerative diseases,such as Parkinson’s disease(PD). Although the precise mechanisms that result in the degeneration of dopaminergic neurons in PD remain unclear,the crucial role of oxidative stress in the pathogenesis of PD is associated with several proteins(such as DJ-1). Our study revealed that hsa-miR-4639-5 p and hsa-miR-617 could suppress the expression of DJ-1 protein through binding 3’-untranslated region(UTR) of DJ-1 mRNA. In vitro studies further demonstrated that hsa-miR-4639-5 p or hsa-miR-617 overexpressed cells were more susceptible to oxidative stress. Q-PCR was used to examine the miRNA levels in the plasma of PD patients,essential tremor patients and healthy controls. Notably,hsa-miR-4639-5 p was significantly up-regulated in the plasma of sporadic PD patients(n=169) compared with healthy controls(n=170) and disease controls(n=60) and maintained relatively high level with disease duration and progression. Thus,it may serve as a potential biomarker for the early diagnosis of PD although both hsa-miR-4639-5 p and hsamiR-617 are involved in the expression of human DJ-1. DJ-1 can protect neurons from oxidative stress,therefore,we supposed that drugs upregulating DJ-1 may relief the stress of neurons in PD,and improve the clinical symptoms. We performed high-throughput screening of small compounds upregulating DJ-1 expression. Firstly,we screened over 8 000 compounds,and get 25 compounds producing over 2 folds increase in signal than negative control. Then,we conducted secondary screening from the 25 compounds,and observed 3 compounds(especially ChemJ) can
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