Department of Neurosciences, University of California San Diego, La Jolla, California, United States of America.
PLoS One. 2011 Jan 31;6(1):e16575. doi: 10.1371/journal.pone.0016575.
Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aβ, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD.
阿尔茨海默病（AD）是一种无法治愈的进行性神经退行性疾病，是痴呆症最常见的形式。由于无法将蛋白质递送到血脑屏障（BBB）内，因此治疗选择一直难以实现。为了提高 AD 的治疗潜力，我们利用了一种有前途的新方法，将蛋白质递送到 BBB 内。我们生成了一种表达淀粉样蛋白β降解酶 Neprilysin 的慢病毒载体，该酶与 ApoB 转运结构域融合，并通过腹腔内注射递送到 AD 的淀粉样蛋白前体（APP）转基因模型中。接受治疗的小鼠的 Aβ水平降低，斑块减少，中枢神经系统中的突触密度增加。此外，用针对中枢神经系统的 Neprilysin 进行治疗的小鼠的记忆缺陷得到了逆转。因此，将 ApoB 转运结构域添加到分泌的 Neprilysin 中，产生了一种非侵入性的治疗方法，可能是 AD 患者的潜在治疗方法。
