Therapeutic Strategies in Alzheimer's Diserase: 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

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 84(2), 101-112, 2000-10-01

    公益社団法人 日本薬理学会

参考文献:  80件中 1-80件 を表示

被引用文献:  1件中 1-1件 を表示

各種コード

  • NII論文ID(NAID)
    10008185341
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    REV
  • ISSN
    00215198
  • NDL 記事登録ID
    5549042
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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