Pathophysiological analysis of essential tremor and identification of the novel therapeutic targets.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21501
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy; General pharmacology
• Research Institution: Osaka University of Pharmaceutical Sciences
• Principal Investigator: Shimizu Saki 大阪薬科大学, 薬学部, 助教 (00630815)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 本態性振戦 / β遮断薬 / aspartoacylase / 脳内モノアミン / セロトニン（5-HT）

Outline of Final Research Achievements

To explore the novel therapeutics of essential tremor, we analyzed the pharmacological mechanism of non-selective β blocker, propranolol, the control therapy against essential tremor, using the spontaneous essential tremor model, Tremor rat. Propranolol inhibited the neural excitation of the inferior olive, the generation site of tremor, which it was the effect via the intracerebral β2 receptors. Also, both Tremor rat and aspartoacylase-KO rat showed enhancement of 5-HT turnover in the inferior olive. In addition, the deletion of aspartoacylase increased the sensitivity of tremor induction. The present study suggests that these targets may be useful for the novel therapeutics for essential tremor.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本態性振戦は高齢者に多く発症する不随意運動障害であり、認知症やパーキンソン病などとの合併症が多く認められる疾患である。手先の不自由を伴う微細運動障害は、患者のQOLに大きな障害となっている。しかし未だ根本的治療薬は存在せず、より有効性の高い新たな治療法の開発が求められてきた。本研究成果は、本態性振戦の発現機序や対症療法であるβ遮断薬の作用機序、脳内5-HT代謝回転と振戦発現との関連性の解明に繋がるものであり、本態性振戦の新規治療法開発における重要な知見が得られたものと考えられる。