Genetical, morphological, and functional analysis of CHMP2B in a patient of familial FTD

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590390
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Niigata University
• Principal Investigator: TOYOSHIMA Yasuko 新潟大学, 脳研究所, 准教授 (20334675)
• Co-Investigator(Kenkyū-buntansha): IKEUCHI Takeshi 新潟大学, 脳研究所, 教授 (20372469) ; TAKAHASHI Hitoshi 新潟大学, 脳研究所, 教授
• Project Period (FY): 2011 – 2013
• Keywords: 前頭側頭葉型認知症 / CHMP2B / オートファジー / ユビキチン陽性封入体 / ALS

Research Abstract

The charged multivesicular body protein 2B gene (CHMP2B) was recently associated with frontotemporal lobar degeneration (FTLD) associated to chromosome 3 in a Danish FTLD family (FTD-3). We report a Japanese family of FTD-3 that developed FTLD in 6members of 3 successive generations. Interestingly, 4 members of 2 successive generations had gastric cancer, and FTLD and gastric cancer cosegregated in the two family members. CHMP2B encode a component of the heteromeric ESCRT-III complex (endosomal sorting complex required for transport III). Dysfunction of the endosomal systems may lead FTLD and cancer.We observed ubiquitin-positive and TDP-43-negative neuronal intracytoplasmic inclusions as previously reported. We could not find any mutation in the CHMP2B gene, however, we observed shorten splicing variant of the m-RNA. The variant showed modified amino acid sequence in the C-terminal.

Research Products

• [Journal Article] TDP-43 pathology in polyglutamine diseases : with reference to amyotrphic lateral sclerosis (2014)
  • Author(s): Toyoshima Y, Takahashi H
  • Journal Title: Neuropathology Volume: 34(1) Pages: 77-82
  • Peer Reviewed
• [Journal Article] Transportin 1 accumulates in FUS inclusions in adult-onset ALS without FUS mutation (2013)
  • Author(s): Takeuchi R, Toyoshima Y, Tada M, Shiga A, Tanaka H, Shimohata M, Kimura K, Morita T, Kakita A, Nishizawa M, Takahashi H
  • Journal Title: Neuropathol Appl Neurobiol Volume: 39(5) Pages: 580-4
  • Peer Reviewed
• [Journal Article] Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene (2013)
  • Author(s): Shimizu H, Toyoshima Y, Shiga A, Yokoseki A, Arakawa K, Sekine Y, Shimohata T, Ikeuchi T, Nishizawa M, Kakita A, Onodera O, Takahashi H
  • Journal Title: Acta Neuropathol Volume: 126(3) Pages: 453-9
  • Peer Reviewed
• [Journal Article] Autophagy-related proteins (p62, NBR1 and LC3) in intranuclear inclusions in neurodegenerative diseases (2012)
  • Author(s): Mori F, Tanji K, Odagiri S, Toyoshima Y, Yoshida M, Kakita A, Takahashi H, Wakabayashi K
  • Journal Title: Neurosci Lett. Volume: 522(2) Pages: 134-8
  • Peer Reviewed
• [Journal Article] Ubiquilin immunoreactivity in cytoplasmic and nuclear inclusions in synucleinopathies, polyglutamine diseases and intranuclear inclusion body disease (2012)
  • Author(s): Mori F, Tanji K, Odagiri S, Toyoshima Y, Yoshida M, Ikeda T, Sasaki H, Kakita A, Takahashi H, Wakabayashi K
  • Journal Title: Acta Neuropathol Volume: 124(1) Pages: 149-51
  • Peer Reviewed