Nicotinic Receptor-Mediated Neuroprotection in Neurodegenerative Disease Models
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- Shimohama Shun
- Department of Neurology, School of Medicine, Sapporo Medical University
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Multiple lines of evidence, from molecular and cellular to epidemiological, have implicated nicotinic transmission in the pathology of Alzheimer's disease (AD) and Parkinson's disease (PD). This review article presents evidence for nicotinic acetylcholine receptor (nAChR)-mediated protection and the signal transduction involved in this mechanism. The data is based mainly on our studies using rat-cultured primary neurons. Nicotine-induced protection was blocked by an α7 nAChR antagonist, a phosphatidylinositol 3-kinase (PI3K) inhibitor, and an Src inhibitor. Levels of phosphorylated Akt, an effector of PI3K, Bcl-2 and Bcl-x were increased by nicotine administration. From these experimental data, our hypothesis for the mechanism of nAChR-mediated survival signal transduction is that the α7 nAChR stimulates the Src family, which activates PI3K to phosphorylate Akt, which subsequently transmits the signal to up-regulate Bcl-2 and Bcl-x. Up-regulation of Bcl-2 and Bcl-x could prevent cells from neuronal death induced by β-amyloid (Aβ), glutamate and rotenone. These findings suggest that protective therapy with nAChR stimulation could delay the progress of neurodegenerative diseases such as AD and PD.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 32 (3), 332-336, 2009
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679601836672
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- NII論文ID
- 110007122754
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 10166168
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- 抄録ライセンスフラグ
- 使用不可