認知症の予防・治療技術開発の新しい戦略<br/>—天然物を用いたアプローチ—

DOI Web Site Web Site PubMed 被引用文献5件 参考文献129件
  • 大泉 康
    東北大学大学院薬学研究科 東北大学大学院工学研究科 静岡県立大学大学院薬学研究科 東北福祉大学感性福祉研究所 横浜薬科大学

書誌事項

タイトル別名
  • A New Strategy for Preventive and Functional Therapeutic Methods for Dementia<br/>—Approach Using Natural Products—
  • 認知症の予防・治療技術開発の新しい戦略 : 天然物を用いたアプローチ
  • ニンチショウ ノ ヨボウ ・ チリョウ ギジュツ カイハツ ノ アタラシイ センリャク : テンネンブツ オ モチイタ アプローチ
  • A New Strategy for Preventive and Functional Therapeutic Methods for Dementia<br/>&mdash;Approach Using Natural Products&mdash;
  • [A new strategy for prevention and finctional therapeutic methods for dementia --approach using natural products]

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抄録

  Alzheimer's disease (AD) has become a serious social problem in Japan. However, effective preventive and fundamental therapeutic methods for AD have not yet been developed. Using a new strategy in the course of our survey of numerous natural resouces having neurotrophic activity, we isolated a variety of active constituents and proved their pharmacological properties. As a result, we successfully found nobiletin, a compound with anti-dementia activity that comes from citrus peels. Also, we have demonstrated that nobiletin ameliorates cognitive impairment in several dementia model animals such as chronically amyloid β(Aβ) infused rats, amyloid precursor protein transgenic (APPTg) mice, olfactory-bulbectomized (OBX) mice, N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801)-treated mice, senescence-accelated mice and bilaterial common carotid arteries occlusion mice. In a APPTg mouse of AD, nobiletin greatly improved memory impairment, and this was accompanied by a marked decrease in Aβ deposition. Also, in OBX mice memory impairment was markedly recoverd by nobiletin, accompanied by improvement of a decrease indensity of cholinergic neurons. Interestingly, nobiletin improves age-related congnitive impairment and decreased hyperphosphorylation of tau as well as oxidative stress in senescence-accelerated mice. In cultured cells, nobiletin reversed the Aβ-induced inhibition of glutamate-induced increases in cAMP response element binding protein (CREB) phosphorylation and modulated gen expression of thioredoxin-interacting protein and NMDA resceptor subunits. These results suggest that nobiletin prevents memory impairment and exhibits a protecting action against neurodgeneration in AD model animals. Nobiletin and citrus peels thus have potential as functional foods for prevention of dementia.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 135 (3), 449-464, 2015

    公益社団法人 日本薬学会

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