2011 Fiscal Year Final Research Report
Adenovirus-mediated inhibition of proteolytic and cell death pathways in adult rat motoneurons.
Project/Area Number |
21500341
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Nerve anatomy/Neuropathology
|
Research Institution | 財団法人東京都医学総合研究所 (2011) Tokyo Metropolitan Organization for Medical Research (2009-2010) |
Principal Investigator |
WATABE Kazuhiko 財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 副参事研究員 (30240477)
|
Project Period (FY) |
2009 – 2011
|
Keywords | 運動ニューロン / TDP-43 / FUS / 筋萎縮性側索硬化症 / アデノウイルス / プロテアソーム / オートファジー / ESCRT |
Research Abstract |
Impairment of proteolytic machineries has been recognized to participate in motoneuron degeneration in ALS. Furthermore, recent identifications of disease-associated genes that include TDP-43 and FUS have led to open a new era in ALS research. We produced recombinant adenovirus encoding wild type and mutant TDP-43 or FUS, and those encoding shRNAs for proteosome(PSMC1), endosome/ESCRT(VPS24) and autophagy(ATG5) systems to investigate whether the coupled gene transductions in motoneurons elicit ALS pathology. Co-infections of adenovirus encoding shRNA for PSMC1 or ATG5 with TDP-43 or FUS adenovirus enhanced cytoplasmic aggregate formation in motoneurons, suggesting that impairment of proteasome, endosome/ESCRT, or autophagy system accelerates TDP-43 and FUS pathology in ALS.
|
-
-
-
-
-
-
-
-
-
[Journal Article] Establishment of an improved mouse model for infantile neuroaxonal dystrophy that shows early disease onset and bears a point mutation in Pla2g62009
Author(s)
Wada H, Yasuda T, Miura I, Watabe K, Sawa C, Kamijuku H, Kojo S, Taniguchi M, Nishino I, Wakana S, Yoshida H, Seino K
-
Journal Title
Am J Pathol
Volume: 175
Pages: 2257-2263
DOI
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-