Analysis of ion channel impairment in the pathogenesis of TTR amyloidosis

• Project/Area Number: 16K19516
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Kumamoto University
• Principal Investigator: Misumi Yohei 熊本大学, 大学院生命科学研究部(医), 助教 (80625781)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アミロイドーシス / トランスサイレチン / イオンチャネル / 横細管 / アミロイド / カルシウムチャネル

Outline of Final Research Achievements

Transthyretin (TTR) amyloidosis is a fatal systemic amyloidosis in which both wild type and mutant TTR form amyloid fibrils. Our pathological analysis revealed that TTR amyloid deposits were deposited mainly in the myocardial transverse tubule where ion channels are abundantly present. The amount of TTR amyloid deposition correlates with the decrease in calcium channel. Analysis using myocardial cell line and fluorescent calcium ion probe showed that TTR amyloid fibrils impairs calcium ion channel function. These data suggest that ion channel failure caused by TTR amyloid deposits is an important pathogenesis of TTR amyloidosis.

Research Products

• [Journal Article] Genetic and clinical characteristics of hereditary transthyretin amyloidosis in endemic and non-endemic areas: experience from a single-referral center in Japan. (2018)
  • Author(s): Yamashita T, Ueda M, Misumi Y, Masuda T, Nomura T, Tasaki M, Takamatsu K, Sasada K, Obayashi K, Matsui H, Ando Y.
  • Journal Title: Journal of Neurology Volume: 265 Issue: 1 Pages: 134-140
  • DOI: 10.1007/s00415-017-8640-7
  • Peer Reviewed / Open Access
• [Journal Article] A novel transthyretin variant V28S (p.V48S) with a double-nucleotide substitution in the same codon. (2017)
  • Author(s): Okada M, Misumi Y, Ueda M, Yamashita T, Masuda T, Tasaki M, Ando Y.
  • Journal Title: Amyloid Volume: 24 Issue: 4 Pages: 231-232
  • DOI: 10.1080/13506129.2017.1381082
  • Peer Reviewed
• [Journal Article] Early skin denervation in hereditary and iatrogenic transthyretin amyloid neuropathy. (2017)
  • Author(s): Masuda T, Ueda M, Suenaga G, Misumi Y, Tasaki M, Izaki A, Yanagisawa Y, Inoue Y, Motokawa H, Matsumoto S, Mizukami M, Arimura A, Deguchi T, Nishio Y, Yamashita T, Inomata Y, Obayashi K, Ando Y
  • Journal Title: Neurology Volume: 88 Issue: 23 Pages: 2192-2197
  • DOI: 10.1212/wnl.0000000000004016
  • Peer Reviewed / Open Access
• [Journal Article] Inflammatory state exists in familial amyloid polyneuropathy that may be triggered by mutated transthyretin. (2017)
  • Author(s): Suenaga G, Ikeda T, Masuda T, Motokawa H, Yamashita T, Takamatsu K, Misumi Y, Ueda M, Matsui H, Senju S, Ando Y.
  • Journal Title: Sci. Rep Volume: 7(1) Issue: 1 Pages: 1579-2017
  • DOI: 10.1038/s41598-017-01775-4
  • Peer Reviewed / Open Access
• [Journal Article] Novel screening for transthyretin amyloidosis by using fat ultrasonography. (2017)
  • Author(s): Misumi Y, Ueda M, Yamashita T, Masuda T, Kinoshita Y, Tasaki M, Nagase T, Ando Y
  • Journal Title: Ann Neurol Volume: 印刷中 Issue: 4 Pages: 604-608
  • DOI: 10.1002/ana.24914
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinicopathological and biochemical findings of thyroid amyloid in hereditary transthyretin amyloidosis with and without liver transplantation. (2017)
  • Author(s): Huang G, Ueda M, Tasaki M, Yamashita T, Misumi Y, Masuda T, Suenaga G, Inoue Y, Kinoshita Y, Matsumoto S, Mizukami M, Tsuda Y, Nomura T, Obayashi K, Ando Y
  • Journal Title: Amyloid Volume: 印刷中 Issue: 1 Pages: 1-6
  • DOI: 10.1080/13506129.2016.1276440
  • Peer Reviewed
• [Journal Article] Involvement of macrophages in the pathogenesis of familial amyloid polyneuropathy and efficacy of human iPS cell-derived macrophages in its treatment. (2016)
  • Author(s): Suenaga G, Ikeda T, Komohara Y, Takamatsu K, Kakuma T, Tasaki M, Misumi Y, Ueda M, Ito T, Senju S, Ando Y
  • Journal Title: PLoS One Volume: 11 Issue: 10 Pages: e0163944-e0163944
  • DOI: 10.1371/journal.pone.0163944
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Knee osteoarthritis associated with different kinds of amyloid deposits and the impact of aging on type of amyloid. (2016)
  • Author(s): Yanagisawa A, Ueda M, Sueyoshi T, Nakamura E, Tasaki M, Suenaga G, Motokawa H, Toyoshima R, Kinoshita Y, Misumi Y, Yamashita T, Sakaguchi M, Westermark P, Mizuta H, Ando Y.
  • Journal Title: Amyloid Volume: 23 Issue: 1 Pages: 26-32
  • DOI: 10.3109/13506129.2015.1115758
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Effects of fibroblasts on the morphology of transthyretin amyloid deposition (2017)
  • Author(s): Misumi Y, Kinoshita Y, Nomura T, Ueda M, Masuda T, Yamashita T, Ando Y
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] ccurrence factors and clinical picture of iatrogenic transthyretin amyloidosis after domino liver transplantation. (2016)
  • Author(s): Misumi Y, Oshima T, Ueda M, Yamashita T, Tasaki M, Masuda, Obayashi K, Ando Y
  • Organizer: XV International Symposium on Amyloidosis
  • Place of Presentation: Uppsala, Sweden
  • Year and Date: 2016-07-03
  • Int'l Joint Research