2000 Fiscal Year Final Research Report Summary
The molecular pathological study on the persephin in neurodegenerative diseases
| Project/Area Number |
11672401
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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 | KYOTO UNIVESITY |
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Principal Investigator |
AKIGUCHI Ichiro Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (30115779)
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| Project Period (FY) |
1999 – 2000
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| Keywords | GDNF / persephin / Parkinson's disease / amyotrophic lateral sclerosis |
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| Research Abstract |
Glial cell line-derived neurotrophic factor(GDNF)is a neurotrophic factor for dopaminergic neurons, which has been uncovered from glial cell line. Recent studies have identified homologous neurotrophic factors termed neurturin and persephin, the amino acid sequences of which show about 49 % homologies with GDNF.Persephin has been found to have trophic effect against the midbrain dopaminergic neurons and anterior horn cells. Furthermore, persephin does not show the trophic effect against the peripheral nerves, suggesting that persephin plays a crucial role in the central nervous system. Thus, we have planned to investigate the possible pathophysiological role of persephin n in the neurodegenerative diseases such as Parkinson's disease and amyotrophic lateral sclerosis, the etiology of which has not to be determined.
We produced synthetic oligopeptides of n-teminal and c-terminal of persephin in 1999. After conjugation of these peptides with KLH using MBS, we immunized New Zealand rabbits by the conjugates for two years. However, we have not got sera of a high titer both by c-terminal peptides and n-terminal peptides. Our previous experiences on the production of anti-NGF antibody and anti-BDNF antibody, twelve immunozations of one month interval produce good antibody. Therefore, additive immunization would not give a good result. Thus, we determined to stop another immunization project. The reason why we have made good results has not yet to be determined. The conformational difference between NGF family and GDNF family might have effect against the efficacy of immunogens. Another possibility is that the intracellular localization of GDNF family and NGF family might be different. We might be able to get antibody using native persephin or recombinant one.
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