Integrated research of polyglutamine disease and ALS/FTLD by analysis of UBQLN2

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293207
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Yokohama City University
• Principal Investigator: TANAKA Fumiaki 横浜市立大学, 医学(系)研究科(研究院), 教授 (30378012)
• Co-Investigator(Kenkyū-buntansha): DOI Hiroshi 横浜市立大学, 医学部, 講師 (10326035) ; KOYANO Shigeru 横浜市立大学, 医学部, 准教授 (50315818) ; TANAKA Ken-ichi 横浜市立大学, 医学部, 助教 (50722881)
• Co-Investigator(Renkei-kenkyūsha): NUKINA Nobuyuki 順天堂大学, 医学研究科, 客員教授 (10134595)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ALS / ポリグルタミン病 / UBQLN2

Outline of Final Research Achievements

We aimed to elucidate the role of UBQLN2 in neurodegeneration of ALS/FTLD and polyglutamine disease. Using mass spectrometry equipment we tried to identify molecules that exhibit differential binding affinity for wild-type and mutant UBQLN2 causing ALS/FTLD. As a result, Hsc71 was identified as one of the proteins showing reduced binding affinity for mutant UBQLN2. Further, we found that binding with Hsc71 depends on PXX domain of UBQLN2. In addition, we created the total and neuron-specific UBQLN2 knockout mice by mating Ubqln2 flox/flox mice with Actb-Cre mice and the Tubb3-Cre mice, respectively.

Free Research Field

神経内科学