外周给予人源化抗朊蛋白（PrP）抗体可阻断阿尔茨海默病β淀粉样蛋白（Aβ）的突触毒性。
Peripheral administration of a humanized anti-PrP antibody blocks Alzheimer's disease Aβ synaptotoxicity.
作者信息
Klyubin Igor, Nicoll Andrew J, Khalili-Shirazi Azadeh, Farmer Michael, Canning Stephanie, Mably Alexandra, Linehan Jacqueline, Brown Alexander, Wakeling Madeleine, Brandner Sebastian, Walsh Dominic M, Rowan Michael J, Collinge John
机构信息
Department of Pharmacology and Therapeutics and Institute of Neuroscience, Trinity College, Dublin 2, Republic of Ireland, Medical Research Council Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, United Kingdom, Laboratory for Neurodegenerative Research, Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Institute of Medicine, Boston, Massachusetts 02115, and Biotherapeutics Group, Medical Research Council Technology, Mill Hill, London, United Kingdom NW7 1AD.
出版信息
J Neurosci. 2014 Apr 30;34(18):6140-5. doi: 10.1523/JNEUROSCI.3526-13.2014.
Abstract
Alzheimer's disease (AD) is associated with pathological assembly states of amyloid-β protein (Aβ). Aβ-related synaptotoxicity can be blocked by anti-prion protein (PrP) antibodies, potentially allowing therapeutic targeting of this aspect of AD neuropathogenesis. Here, we show that intravascular administration of a high-affinity humanized anti-PrP antibody to rats can prevent the plasticity-disrupting effects induced by exposure to soluble AD brain extract. These results provide an in vivo proof of principle for such a therapeutic strategy.
摘要
阿尔茨海默病（AD）与β淀粉样蛋白（Aβ）的病理组装状态相关。抗朊蛋白（PrP）抗体可阻断与Aβ相关的突触毒性，这可能为针对AD神经病理发生这一方面的治疗提供靶点。在此，我们表明向大鼠血管内注射高亲和力人源化抗PrP抗体可预防暴露于可溶性AD脑提取物所诱导的可塑性破坏效应。这些结果为这种治疗策略提供了体内原理证明。
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The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein.抗朊病毒抗体的毒性是由朊病毒蛋白的柔性尾巴介导的。
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Amyloid-β-induced synapse damage is mediated via cross-linkage of cellular prion proteins.淀粉样β诱导的突触损伤是通过细胞朊病毒蛋白的交联介导的。
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Alzheimer's disease brain-derived amyloid-β-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein.阿尔茨海默病脑源性淀粉样蛋白-β在体内介导的 LTP 抑制可被针对细胞朊病毒蛋白的免疫靶向所预防。
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