2013 Fiscal Year Final Research Report
Elucidation of mechanism underlying accelerated production of endogenous aldehyde in amyotrophic lateral sclerosis and development of new drug therapy
| Project/Area Number |
23590650
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Nihon University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Keywords | 筋萎縮性側索硬化症 / 運動ニューロン / N-acetyl-L-cysteine / 4-Hydroxynonenal / PGE2 |
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| Research Abstract |
Higher levels of 4-Hydroxynonenal (HNE) have been shown in the cerebrospinal fluid of amyotrophic lateral sclerosis (ALS) patients and mice models of ALS. In this study, we investigated phathophysiological roles of HNE in ALS and protective potentials of N-acetyl-L-cysteine (NAC) and its derivative, NAC-amide (NACA) in a mouse model of ALS (G93A). The levels of HNE-modified proteins in the spinal cord of the G93A were significantly increased at 15 weeks (onset of motor disturbance) and older. Administration of NAC had no effect on disease progression and survival in the G93A. In contrast, administration of NACA slowed disease progression and prolonged survival in these mice. These results suggest that HNE may play a role in the degeneration of motoneurons in the G93A, and that NACA is a promising therapeutic drug for ALS.
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[Journal Article] New insights into the mechanism of neurolathyrism : L-β-ODAP triggers [Ca^2+]i accumulation and cell death in primary motor neurons through transient receptor potential channels and metabotropic glutamate receptors2014
Author(s)
Kusama-Eguchi K, Miyano T, Yamamoto M, Suda A, Ito Y, Ishige K, Ishii M, Ogawa Y, Watanabe K, Ikegami F, Kusama T
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Journal Title
Food Chem Toxicol
Volume: 67
Pages: 113-122
Peer Reviewed
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