PII-008 - MICRORNA REGULATING SEL1L INVOLVED IN THE PATHOGENESIS OF PARKINSON'S DISEASE AND ITS EXPRESSION LEVELS IN PATIENT PLASMA.

T. Omura^1,2, L. Nomura², H. Nishiguchi¹, H. Kaneda¹, Y. Kitahiro¹, K. Itohara¹, A. Tanaka³, T. Furubayashi³, K. Yamamoto^1,4, T. sakane³, K. Matsubara^5,2, I. Yano¹; ¹Department of Pharmacy, Kobe University Hospital, Kobe, Japan, ²Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan, ³Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Kobe, Japan, ⁴Department of Integrated Clinical and Basic Pharmaceutical Science, Okayama University, Okayama, Japan, ⁵School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.

Background: The apoptosis of dopaminergic neurons caused by endoplasmic reticulum (ER) stress has been reported as a mechanism involved in the pathogenesis of Parkinson’s disease (PD). We previously reported that SEL1L, a molecule associated with ER stress, is one of the key molecules related to onset of PD. Recently, microRNAs (miRNAs) have been implicated in the development of neurodegenerative disorders including PD. In this study, we explored miRNAs that regulate SEL1L and investigated whether these miRNAs influence the expression levels of SEL1L and cell death in the PD model generated by 6-hydroxydopamine. Additionally, we examined the expression levels of miRNA in the plasma of both healthy individuals and PD patients.

Methods: We searched four public databases to explore miRNAs that regulate SEL1L expression. We then investigated whether the identified miRNAs affect SEL1L expression levels and cell death in the PD model using real-time PCR, Western blotting, and MTT assay. In addition, miRNAs were extracted from the plasma of healthy individuals and PD patients, and the expression levels of miRNA were analyzed using real-time PCR.

Results: MiR-101 was identified as the miRNA that regulates SEL1L by the database analysis, as well as the expression levels in the PD model and luciferase reporter analysis. When the expression levels of miR-101 were upregulated by the miR-101 mimic transfection in the cellular PD model, and the SEL1L levels were suppressed and neuronal cell death was enhanced. The result obtained from plasma analysis revealed that miR-101 expression was lower in PD patients than in healthy individuals.

Conclusion: We demonstrated that miR-101 influences neuronal cell death in the PD model by regulating SEL1L expression. Additionally, lower miR-101 levels in PD patients may lead to higher SEL1L expression, potentially offering some resistance to dopaminergic neuronal cell death in the substantia nigra. MiR-101 may have the potential to serve as both a new pharmacotherapeutic target and a diagnostic biomarker for PD.