Inhibition of clathrin-mediated endocytosis prevents amyloid β-induced axonal damage

Neurobiology of Aging
Tomoharu KuboyamaChihiro Tohda

Abstract

Amyloid β (Aβ)-induced axonal degeneration is a major cause of Alzheimer's disease (AD) pathology. However, the critical target to prevent Aβ-induced axonal degeneration remains unknown. Here, we analyzed growth cone collapse elicited by Aβ, a putative early Aβ-induced event in axons. Although no study has yet shown influence of Aβ on the growth cone, we first visualized Aβ-initiated growth cone collapse in cultured neurons. Furthermore, we determined that the collapse was triggered by clathrin-mediated endocytosis probably via Aβ-Ca(2+) signaling. The inhibition of clathrin-mediated endocytosis prevented Aβ-induced axonal loss both in vitro and in vivo and prevented memory impairment in an AD mouse model. Our results clarified the important role of clathrin-mediated endocytosis in Aβ-induced collapse of growth cone that leads to axonal degeneration and memory impairment.

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Citations

May 19, 2018·Journal of Molecular Neuroscience : MN·Xue FuYang Lü
Feb 16, 2019·Phytotherapy Research : PTR·Zhiyou YangChihiro Tohda
Aug 15, 2018·Journal of Alzheimer's Disease : JAD·Olga ZolochevskaGiulio Taglialatela
Nov 7, 2019·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Tomoharu Kuboyama
Apr 21, 2017·Frontiers in Molecular Neuroscience·Haixia HuMingliang Xiang
Mar 7, 2021·Molecular Neurobiology·Lei ZhangYu Deng
Apr 29, 2021·Journal of Cell Science·Tatiana BurrinhaCláudia Guimas Almeida
Dec 21, 2017·Langmuir : the ACS Journal of Surfaces and Colloids·Aune KoitmäeRobert H Blick

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