Intranasal neprilysin rapidly eliminates amyloid-beta plaques, but causes plaque compensations: the explanation why the amyloid-beta cascade may fail?

作     者：Christian Humpel Christian Humpel

作者机构：Laboratory of Psychiatry and Experimental Alzheimer’s ResearchMedical University of InnsbruckInnsbruckAustria 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2022年第17卷第9期

页      面：1881-1884页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100203[医学-老年医学] 10[医学] 

主　　题：amyloid-beta amyloid-beta degrading enzyme clear plaque collagen biomaterial intranasal neprilysin nose-to-brain 

摘      要：Neurodegenerative brain disorders are a major burden in our society,such as Alzheimer´s disease.In order to repair or prevent such diseases,drugs are designed which enter the brain,but the blood-brain barrier limits their entry and the search for alternative pathways is important.Recently,we reported that intranasal delivery of the amyloid-beta degrading enzyme neprilysin eliminated amyloid-beta plaques in transgenic Alzheimer´s disease mice.This review describes the anatomical structure of the intranasal pathway,explains the intranasal delivery of pure neprilysin,cell-loaded neprilysin(platelets)and collagen-embedded neprilysin to destruct amyloid-beta plaques in Alzheimer´s disease in transgenic APP_SweDI mice and hypothesizes why this may cause compensation and why the amyloid-beta cascade hypothesis may fail.