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演題詳細

Oral

アルツハイマー病、他の認知症、老化 3
Alzheimer's Disease, Other Dementia, Aging 3

開催日 2014/9/12
時間 15:00 - 16:00
会場 Room I(311+312)
Chairperson(s) 玉岡 晃 / Akira Tamaoka (筑波大学医学医療系神経内科学 / Department of Neurology, University of Tsukuba, Japan)
田口 明子 / Akiko Taguchi (宮崎大学医学部神経呼吸内分泌代謝学分野 / Department of Neurology, Respirology, Endocrinology and Metabolism, Miyazaki University School of Medicine, Japan)

アミロイドβタンパクによるBACE1の発現亢進
BACE1 expression is enhanced by amyloid β-protein

  • O2-I-3-2
  • 荒木 亘 / Wataru Araki:1 保坂 愛 / Ai Hosaka:2 儘田 直美 / Naomi Mamada:1,2 田之頭 大輔 / Daisuke Tanokashira:1 玉岡 晃 / Akira Tamaoka:2 
  • 1:国立精神・神経医療研究センター神経研究所 / Nat'l Inst.of Neurosci., NCNP, Tokyo, Japan 2:筑波大学神経内科 / Dept Neurol, Univ of Tsukuba, Tsukuba, Japan 

β-Secretase BACE1 is a membrane-bound protease that is essential for the production of amyloid β-protein (Aβ). Recent evidence suggests that oligomeric forms of Aβ play a primary pathogenic role in Alzheimer's disease (AD). The fact that the expression of BACE1 is increased in the brains of AD patients as well as AD model mice implicates that BACE1 expression is influenced by Aβ. In the present study, we investigated whether and how treatment of cultured neurons with Aβ42 alters BACE1 expression. We treated rat primary cerebral cortical neurons with Aβ oligomers or fibrils (2.5 μM) for 2-3 days, and analyzed the expression levels of BACE1 and other proteins by Western blot anaysis. We found that protein expression levels of BACE1, but not those of amyloid precursor protein (APP), were significantly increased in neurons treated with Aβ oligomers, compared with control untreated neurons. Levels of APP C-terminal fragments were also increased in Aβ-treated neurons, suggesting enhanced amyloidogenic processing of APP. Furthermore, Aβ-treated neurons exhibited significantly elevated levels of phosphorylated eIF2α, compared with control neurons. These data demonstrated that Aβ42 oligomers can enhance BACE1 expression in neurons. The enhancement of BACE1 expression may occur at the translational level via activation of eIF2α. Thus, a vicious cycle may exist, wherein Aβ augments its own production through enhancement of neuronal BACE1 expression.

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