Analysis of TFG gene and development of treatment for motor neuron diseases

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461294
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: The University of Tokushima
• Principal Investigator: KAWARAI Toshitaka 徳島大学, 大学院医歯薬学研究部(医学系), 講師 (50614137)
• Co-Investigator(Renkei-kenkyūsha): IMOTOI Issei 徳島大学, 大学院医歯薬学研究部, 教授 (30258610) ; TAJIMA Atsushi 金沢大学, 医学系, 教授 (10396864)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 運動ニューロン病 / TFG

Outline of Final Research Achievements

We performed biological characterization of neural cells derived from hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) patient induced pluripotent stem cells (iPSCs), and revealed proteasome dysfunction when the iPSCs carrying the clinical mutation, Pro285Leu, in tropomyosin-receptor kinase fused gene (TFG). We also analyzed the animal model for HMSN-P, transgenic mice over expressing human mutant TFG, and demonstrated replication of intraneuronal aggregations, including TFG, optineurin, and TAR DNA binding protein 43 (TDP-43). The model mice are undergoing therapeutic trial using phenylbutyrate, which has been demonstrated to be clinically and pathologically effective to decrease Tau aggregation in transgenic mice via activation of autophagy.

Free Research Field

臨床神経科学