The Absence of Myelin Basic Protein Reduces Non-Amyloidogenic Processing of Amyloid Precursor Protein

doi:10.2174/1567205018666210701162851

摘要

背景：淀粉样 β 蛋白 (Aβ) 在大脑中的积累是阿尔茨海默病 (AD) 的病理特征。 Aβ 肽来源于淀粉样前体蛋白 (APP)。 APP 可以通过淀粉样蛋白生成或非淀粉样蛋白生成途径进行蛋白水解切割。 APP 代谢/加工的分子效应可能受 AD 患者和 AD 病理小鼠模型中髓鞘和髓鞘碱性蛋白 (MBP) 分解的影响。

方法：我们直接测试了 MBP 是否可以改变 MBP-/- 小鼠（称为 Shiverer (shi/shi) 小鼠）中的 APP 加工，其中由于 MBP 外显子 ll 中间的基因断裂，没有产生功能性 MBP。

结果：发现 Shiverer (shi/shi) 小鼠的大脑 sAPPα 水平显着降低，尽管总 APP 和 sAPPβ 的水平保持不变。 sAPPα 的减少被认为是由于去整合素和金属蛋白酶 9 (ADAM9) 催化和 APP 的非淀粉样蛋白基因加工的表达水平发生变化，因为它与 ADAM9 结合。 MBP -/- 小鼠表现出增加的 Aβ 寡聚体产生。

结论：这些发现表明，在不存在 MBP 的情况下，非淀粉样蛋白生成的 APP 向 sAPPα 的加工显着减少，靶向少突胶质细胞髓鞘可能是预防和治疗 AD 的一种新疗法。

关键词: 阿尔茨海默病 (AD)、髓鞘碱性蛋白 (MBP)、

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DOI https://dx.doi.org/10.2174/1567205018666210701162851	Print ISSN 1567-2050
Publisher Name Bentham Science Publisher	Online ISSN 1875-5828

当代阿耳茨海默病研究

髓鞘碱性蛋白的缺失减少了淀粉样前体蛋白的非淀粉样加工

摘要

当代阿耳茨海默病研究

髓鞘碱性蛋白的缺失减少了淀粉样前体蛋白的非淀粉样加工

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