HTRA2 blocking peptide

Introduction: In order to better understand the role of epigenetic influences in the etiology of Parkinson's disease (PD), we studied the expression of microRNAs in gyri cinguli of patients and controls. Methods: Expression profiling of 744 well-characterized microRNAs in gyri cinguli from patients and controls using TaqMan array microRNA cards. Verification of significantly dysregulated microRNAs by SYBR Green qRT-PCR. Results: First screen by TaqMan array identified 43 microRNAs that were upregulated in gyri cinguli from patients. Of those microRNAs, 13 are predicted to regulate at least one of six genes mutated in monogenic forms of PD (DJ-1, PARK2, PINKI, LRRK2, SNCA, and HTRA2). Five of these 13 microRNAs (-144,-199b,-221, -488,-544) were also found upregulated by SYBR Green qRT-PCR and are predicted to regulate either SNCA, PARK2, LRRK2 or combinations thereof. Consistently, expression of SNCA, PARK2, and LRRK2 was reduced in patients. An additional 5 out of ten potential target genes tested were downregulated. These are DRAM (DNA damage regulated autophagy modulator 1), predicted to be regulated by miR-144, EVC (Ellis Van Creveld Protein) by miR-221, ZNF440 (Zinc Finger Protein 440) by miR-199b, MTFMT (Mitochondrial Methionyl-tRNA Formyltransferase) by miR-488 and XIRP2 (Xin Actin Binding Repeat Containing) possibly controlled by miR-544a. Conclusion: The study identified five microRNAs that play a role in the etiology of Parkinson's disease likely by modifying expression of SNCA, PARK2, LRRK2 and additional genes required for normal cellular function. (C) 2016 Elsevier Ltd. All rights reserved.

Endoplasmic reticulum (ER) stress has been shown to be associated with the pathogenesis of neurodegenerative disorders including Parkinson's disease (PD). HtrA2/Omi, from its participation in protein quality control, is involved in ER stress. However, little is known about the relationship between HtrA2/Omi and ER stress in PD. Here, we explored the association of HtrA2/Omi and ER stress in a cell model of PD and found that the expression level of HtrA2/Omi decreased with ER stress induction in 6-OHDA-treated SH-SY5Y cells. Furthermore, silencing endogenous expression of HtrA2/Omi with siRNA resulted in aggregated ER stress and cell death. Taken together, our results show that HtrA2/Omi may exert a protective function in 6-OHDA-induced cell death by regulating ER stress-related proteins. This research offers some clues as why mutations in HtrA2/Omi lead to higher susceptibility in some PD patients.