早期动物起源的BACE1 APP/Aβ 蛋白质分解功能
James A Langeland1, Lillian Baumann1, Eva M DeYoung1
1Department of Biology, Kalamazoo College, 1200 Academy Street, Kalamazoo, MI 49006, USA.
Biology
|May 24, 2024
概括
涉及阿尔茨海默病的BACE1酶,可能在动物起源附近进化了其粉样蛋白前体蛋白 (APP) 和β-粉样蛋白 (Aβ) 分裂功能. 这种特定的蛋白质分解活性在它的基质APP进化之前出现了数亿年.
科学领域:
- 进化生物学是进化的生物学.
- 神经科学是一个神经科学.
- 生物化学 生物化学
背景情况:
- 阿尔茨海默病涉及到大脑中的β-粉样蛋白 (Aβ) 积累.
- Aβ是由像BACE1.1这样的酶对粉样蛋白前体蛋白 (APP) 的蛋白解产生.
- BACE1是Aβ生产中的速度限制酶和治疗点.
研究的目的:
- 为了研究BACE1蛋白质分解功能的进化起源和时间.
- 了解BACE1何时在APP/Aβ处理中演变为其特定作用.
主要方法:
- 功能性进化方法检查了早期动物血统中的BACE1正义词.
- 测试BACE1从类动物 (Hydra) 中的APP/Aβ裂变活性.
- 分析了来自昆虫 (Mnemiopsis) 和小 (Monosiga) 的BACE1/2基因.
主要成果:
- 最基本的BACE1正向体在 cnidarians 中被发现.
- 科尼达的BACE1 (来自Hydra) 证明了分裂APP和释放Aβ的能力.
- 来自光体和鞭状体的更多不同的BACE1/2基因缺乏这种特定的蛋白质分解活性.
- BACE1很可能是从动物类基底附近的基因复制事件进化而来的.
结论:
- BACE1的特定蛋白质分解功能是在动物早期多样化过程中演变的.
- 这个功能在它的基质,APP/Aβ的进化之前已经存在了数亿年.
- BACE1的APP/Aβ分裂功能的起源可以追溯到早期的动物进化时期.
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