陳皮の抗認知症成分ノビレチンによるアミロイドβペプチド(Aβ)の神経毒性発現抑制とAβ誘発性記憶障害改善
スポンサーリンク
概要
- 論文の詳細を見る
Alzheimers disease (AD) has become a major health burden to society. However, no fundamentally therapeutic drugs for AD have been developed. Increasing evidence suggests that the elevation of β-amyloid (Aβ) peptides in the brain is central to AD pathogenesis. Recently, in the course of our survey of substances having anti-dementia activity from natural resources, we have successfully found nobiletin, a polymethoxylated flavone contained in AURANTII NOBILIS PERICARPIUM which is a component of traditional Chinese medicines. In this review, we describe the beneficial effects of nobiletin on memory impairment and Aβ pathology in a transgenic mouse model introduced human “Swedish” and “London” mutant amyloid precursor protein. We also note the possible molecular mechanism underlying the protective action against Aβ-induced memory impairment provided by our studies using cultured hippocampal neurons. Namely, daily administration of nobiletin for four months rescued the memory impairment in fear conditioning, and decreased hippocampal Aβ deposit in the transgenic mice as analyzed by immunohistochemistry. PKA-dependent signaling and membrane trafficking of AMPA receptor subunit, GluR1, which are known to be required for long-term potentiation (LTP), have been demonstrated to be inhibited by a sublethal concentration of Aβ in cultured hippocampal neurons. Our in vitro studies evidently showed that a sublethal concentration of Aβ actually inhibited glutamate-induced increases in both PKA substrates phosphorylation and GluR1 membrane trafficking in cultured hippocampal neurons, whereas nobiletin reversed the Aβ-induced inhibition of such biochemical processes. The natural compound with these unique actions has thus potential to become a novel drug for fundamental treatment of AD.
著者
-
大泉 康
横浜薬科大学 漢方薬学科
-
山國 徹
東北大学大学院薬学研究科分子生物薬学分野
-
山國 徹
東北大学大学院薬学研究科薬物療法学分野
-
中島 晶
東北大学大学院薬学研究科
-
大泉 康
横浜薬科大学
-
山國 徹
東北大学大学院薬学研究科
関連論文
- 陳皮の抗認知症成分ノビレチンによるアミロイドβペプチド(Aβ)の神経毒性発現抑制とAβ誘発性記憶障害改善
- Shishihakuhito, a traditional Chinese medicine for atopic dermatitis, inhibits IgE-mediated histamine release from rat RBL-2H3 basophilic leukocyte cells
- 陳皮の抗認知症成分 nobiletin の薬理作用とその機能性食品開発への応用
- ドーパミン神経細胞シナプス小胞におけるシグマ-1受容体の機能
- 海馬スライスにおいてPKA依存的シグナル伝達を促進する nobiletin はAβ誘発性記憶障害を改善する
- 柑橘類成分F-1の記憶・学習障害改善作用とそのメカニズム
- 海馬スライスにおける陳皮成分 nobiletin のLTP誘導作用
- CREBを活性化するノビレチンはNMDA受容体遮断薬により誘発される記憶・学習障害を改善する
- ERKを活性化するノビレチンのNMDA受容体遮断薬誘発性記憶・学習障害に対する改善効果 (第16回 天然薬物の開発と応用シンポジウム講演要旨集)
- 陳皮の抗アルツハイマー病活性成分ノビレチン : アルツハイマー病の新しい予防法と根本治療法の確立を目指して