Pathological roles of dentatorabral-pallidoluysian atrophy (DRPLA) protein in DRPLA brain tissue
| Project/Area Number |
11670652
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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 | Okinaka Memorial Institute for Medical Research |
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Principal Investigator |
YAZAWA Ikuru Okinaka Memorial Institute for Medical Research, 研究員 (20312217)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | dentatonihral-pallidoluysian atrophy / DRPLA / DRPLA gene product / DRPLA protein / poly glutamine / ubiquitin / DRPLA protein complex / anti-DRPLA protein antibody / ユビキチン / 高分子複合体 / ユビキチン化 |
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| Research Abstract |
The number of patients afflicted with type 2 diabetes has risen sharply in Japan these ten to twenty years, at least partly because of a westernization of eating habit and of a sedentary life style. Previously, it was thought that genes involved in the pathogenesis of impaired insulin secretion are more important than those involved in the development of insulin resistance in Japanese. Recent observations, however, suggest that those genes responsible for the development of insulin resistance or obesity are as important. We extracted genomic DNA from unrelated Japanese patients with type 2 diabetes mellitus. We investigated for an association of polymorphisms, which have been reported to be present near candidate genes for the development of type 2 diabetes mellitus. We also investigated for a possible association of those genetic variants, identified by us, with type 2 diabetes mellitus in Japanese. We could not find a significant association of the genetic variants, with type 2 diabe
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tes mellitus. Increased number of DNA samples seems to be necessary to identify susceptible genes for the development of diabetes mellitus.
Glutamine-repeat (Polyglutamine) diseases are a group of hereditary neurodegenerative disorders caused by expansion of a glutamine repeat in responsible gene products. This group includes Huntington s disease (HD) and dentatorubral-pallidoluysian atrophy (DRPLA). Neuronal intranuclear and cytoplasmic inclusions showing immunoreactivity with the gene product are found in brain tissues of patients with HD and DRPLA. Aggregation of the gene products that carry an expanded glutamine repeat seems to be a primary pathological mechanism in glutamine-repeat diseases, although the precise relationship between aggregation and neuronal degeneration is unclear. Our studies of DRPLA demonstrated that several disease processes arising from abnormal protein complex formation involving the DRPLA gene product (DRPLA protein) occur in brain tissues of patients with DRPLA based on immunoblotting data obtained by electrophoresis under non-reducing conditions. The first process is large complex formation due to abnormally strong bonding between DRPLA protein molecules. The second is pathological ubiquitination of the DRPLA protein complex. Immunoblotting studies using anti-phosphoserine antibody and enzymatic dephosphorylation of isolated DRPLA protein complexes recently enabled us to demonstrate that DRPLA protein complexes are aberrantly phosphorylated in DRPLA brain tissues as the third disease process. Less
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Report
(4 results)
Research Products
(15 results)
