| Project/Area Number |
16590835
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kumamoto University |
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Principal Investigator |
UYAMA Eiichiro Kumamoto University School of Medicine, Graduate Scholl of Medicine, Neurology Advanced Biomedical Sciences, Assistant Professor, 医学部附属病院, 講師 (90185075)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | OPMD / PABPN1 / polyalanine disease / OPMD cell model / OPMD model mouse / intranuclear inclusion / rimmed vacuoles / reduction of IN aggregation and cell death / PABPN1核内凝集 / ポリグルタミン病 / コンゴーレッド / OPMDモデルマウス / トレハロース / PABPN1核内凝集体 / GCGリピート / ポリアラニン / 縁取り空胞 / 嚥下障害 / DMRV / コンドーレッド / HSP70 / 細胞死抑制効果 |
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| Research Abstract |
[Back ground] Oculopharyngeal muscular dystrophy (OPMD) is a late-onset polyalanine disorder characterized by progressive ptosis, dysphagia, and limb weakness. Intranuclear, inclusions and rimmed vacuoles are pathological hallmarks. It is caused by heterozygous expansion of a 10-alanine, stretch to 12-17 alanine residues in the N-terminus of the PABPN1. [Purpose] To elucidate its molecular pathogenesis" and to establish its therapy, we performed 1) microarray analyses using gene chip including, 36000 kinds of mRNA for the muscle samples from OPMD model mice A13 and control mice. 2) therapeutic trials to prevent intranuclear aggregation of PABPN1 and cell death using congo red and doxyclcline, which can reduce amyloid aggregation for cell model of OPMD.3) immunohistochemical studies using various antibodies for muscular glycoproteins for the purpose of clarification of rimmed vacuoles formation in OPMD and its related disorder, distal myopathy with rimmed vacuoles (DMRV). [Results] 1)We found various 120 genes that related OPMD with down gegulation. We have continued to further studies to identify OPMD-related genes. 2) Aggregate formation and cytotoxicity in cell models of OPMD were reduced by Congo red or doxycycline. 3) We found that Aracchis hypoganea agglutinin (PNA) lectin reacted strongly with sarcolemmal glycoproteins in the DMRV patients but not with those in conrol subjects including OPMD. We clarified that impaired sialyl 0-glycan formation in muscular glycoproteins, including α-dystroglycan, occurs in DMRV.
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