Therapeutic Strategies in Alzheimer’s Disease: Ml Muscarinic Agonists
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- Fisher Abraham
- Israel Institute for Biological Research,P.O.Box 19,74100 Ness-Ziona,Israel
書誌事項
- タイトル別名
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- Therapeutic Strategies in Alzheimer's Disease. M1 Muscarinic Agonists.
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The cholinergic hypofunction in Alzheimer’s disease(AD)appears to be linked with two other major hallmarks of this disease, β−amyloid and hyperphosphorylated tau protein.Formation of β−amyloids might impair the coupling of M1 muscarinic acetylcholine receptors(mAChR)with G−proteins.This can lead to decreased signal transduction, a decrease of trophic and non−amyloidogenic amyloid precursor protein(APPs)and generation of more β−amyloids, aggravating further the cholinergic deficiency.This review is an attempt to explore the M1 mAChR regulation of β−amyloid metabolism, tau hyperphosphorylation and cognitive functions.The therapeutic potential of M1−selective muscarinic agonists including AF102B, AF150(S), AF267B(the AF series)is evaluated and compared, when possible, with several FDA−approved acetylcholinesterase inhibitors.These M1 agonists can elevate APPs, decrease tau protein phosphorylation/hyperphosphorylation in vitro and in vivo and restore cognitive impairments in several animal models for AD.Except for the M1 agonists, no other compounds were reported yet with combined effects;e.g., amelioration of cognition dysfunction and beneficial modulation of APPs/β−amyloid together with tau hyperphosphorylation/phosphorylation.This property of M1 agonists to alter different aspects associated with AD pathogenesis could represent the most remarkable clinical value of such drugs.
収録刊行物
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- Jpn.J.Pharmacol.
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Jpn.J.Pharmacol. 84 (2), 101-112, 2000
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001204287549696
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- NII論文ID
- 10008185341
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- NII書誌ID
- AA00691188
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- COI
- 1:CAS:528:DC%2BD3cXnvVGgsbc%3D
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- ISSN
- 13473506
- 00215198
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- NDL書誌ID
- 5549042
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- PubMed
- 11128032
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- Web Site
- https://ndlsearch.ndl.go.jp/books/R000000004-I5549042
- https://api.elsevier.com/content/article/PII:S0021519819305219?httpAccept=text/xml
- https://api.elsevier.com/content/article/PII:S0021519819305219?httpAccept=text/plain
- https://www.jstage.jst.go.jp/article/jjp/84/2/84_2_101/_pdf
- https://search.jamas.or.jp/link/ui/2001050511
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- 本文言語コード
- en
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- JaLC
- NDL
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