Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease

Norimichi Nakamura, Yasumasa Ohyagi, Tomohiro Imamura, Yuki T. Yanagihara, Kyoko M. Iinuma, Naoko Soejima, Hiroyuki Murai, Ryo Yamasaki, Jun Ichi Kira

研究成果: ジャーナルへの寄稿記事

7 引用 (Scopus)

抜粋

Apomorphine (APO) promotes intraneuronal amyloid-β (Aβ) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn® to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aβ, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO. Protein levels of two types of serine-phosphorylated insulin receptor substrate-1 (IRS-1), pS616 and pS636/639, significantly decreased following APO treatment in the 13-month-old 3xTg-AD mice brain, suggesting improved brain insulin resistance. Immunostaining of the IDE, pS616 and pS636/639 IRS-1 demonstrated similar changes due to APO treatment. Thus, brain insulin resistance is considered an important therapeutic target in AD, and APO may provide improved neuronal insulin resistance.

元の言語英語
ページ(範囲)1151-1161
ページ数11
ジャーナルJournal of Alzheimer's Disease
58
発行部数4
DOI
出版物ステータス出版済み - 1 1 2017

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

これを引用

Nakamura, N., Ohyagi, Y., Imamura, T., Yanagihara, Y. T., Iinuma, K. M., Soejima, N., ... Kira, J. I. (2017). Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease. Journal of Alzheimer's Disease, 58(4), 1151-1161. https://doi.org/10.3233/JAD-160344