比PROTAC应用更广泛的溶酶体降解技术的发展和挑战( 四 ) 靶向蛋白质降解技术是近十年

04 CMA
Life Biosciences是一家针对衰老生物学的先驱生命科学公司， 2021年4月发表其临床前研究[15] ，证明其伴侣介导的自噬激活剂平台在阿尔茨海默病小鼠模型中的临床益处。这项研究表明，即使在出现神经功能障碍之后，在两种不同的阿尔茨海默病小鼠模型中，使用Life Biosciences的一种工具口服化合物上调CMA也能显着改善神经功能并减少不溶性蛋白质聚集体的积累。

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展望
【比PROTAC应用更广泛的溶酶体降解技术的发展和挑战】LYTAC技术通过靶向内吞-溶酶体途径，降解胞外蛋白和膜蛋白；此外， CMA嵌合体、AUTAC和ATTEC等通过靶向自噬途径的蛋白质降解技术，能够降解错误折叠蛋白、蛋白多聚体或受损细胞器，未来有希望在神经退行性疾病和代谢性疾病的治疗上得以应用。尽管每种技术都有其优点和缺点，新兴的降解技术还处于初级发展阶段。期待溶酶体降解技术能够像PROTAC一样，早日进入临床开发阶段，如果真能实现胞外、膜结合、胞内蛋白灵活降解，或将带来医学领域的颠覆性突破。
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