＜シンポジウム02―1＞アルツハイマー病の分子治療戦略：新しい視点を求めて
細胞内アミロイドβおよび酸化ストレスを標的とする治療薬：アポモルフィン
大八木 保政
九州大学大学院医学研究院内科学講座神経内科学〔〒812―8582 福岡市東区馬出3―1―1〕
Alzheimer's disease (AD) is the major cause of dementia in the elderly people. In the molecular pathogenesis of AD, toxicity of secreted amyloid-β protein (Aβ), especially Aβ oligomers, is considered to play a pivotal role. While, we have long been focused on intraneuronal Aβ as a therapeutic target in AD. Intraneuronal Aβ accumulation is found in the early stage of AD neurons, and may be quite toxic and pathogenic. Recently, we have found apomorphine (APO), a kind of dopamine receptor agonists, to promote the intracellular Aβ degradation activating the Aβ-degrading enzymes, proteasome and insulin-degrading enzyme (IDE). We then found that APO treatment improved memory function and AD-related pathology in an AD mouse model, 3xTg-AD mice. Moreover, APO protected against oxidative stress in vitro and in vivo. We further investigated effects of APO on cellular antioxidative stress system, and found that APO activated glutathione peroxidase (GPx) specifically. Thus, APO may be a promising drug for the cure of AD and clinical trials are necessary in the future. In addition, further investigation to understand the molecular mechanism associated with the APO effect greatly contributes to the development of new drugs for AD.
Full Text of this Article in Japanese PDF (503K)
(臨床神経, 51：884−887, 2011)
key words：アルツハイマー病，3xTg-ADマウス，アポモルフィン，アミロイドβ蛋白，酸化ストレス
（受付日：2011年5月19日）
