Myo1d promotes alpha-synuclein transfer from brain microvascular endothelial cells to pericytes through tunneling nanotubes

Qingrui Duan; Qingxi Zhang; Kun Nie; Rui Huang; Jianhua Yang; Peikun He; Zihui Tie; Haifeng Huang; Guixian Ma; Yuhu Zhang; Yuyuan Gao; Lijuan Wang

doi:10.1016/j.isci.2023.107458

Myo1d promotes alpha-synuclein transfer from brain microvascular endothelial cells to pericytes through tunneling nanotubes

iScience. 2023 Jul 22;26(8):107458. doi: 10.1016/j.isci.2023.107458. eCollection 2023 Aug 18.

Authors

Qingrui Duan^{1

2

3}, Qingxi Zhang^{2

3}, Kun Nie^{2

3}, Rui Huang^{2

3}, Jianhua Yang^{2

3}, Peikun He^{2

3}, Zihui Tie^{2

3}, Haifeng Huang^{2

3}, Guixian Ma^{2

3}, Yuhu Zhang^{2

3}, Yuyuan Gao^{2

3}, Lijuan Wang^{1

2

3}

Affiliations

¹ School of Medicine, South China University of Technology, Guangzhou 510006, China.
² Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
³ Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.

Abstract

α-Synuclein preformed fibrils (α-syn PFF) in the blood can cross the blood-brain barrier and invade the central nervous system. Our previous study proved that α-syn PFF can be taken up by brain microvascular endothelial cells (BMVECs). Here, we found that α-syn PFF spread from BMVECs to pericytes with the highest transmission efficiency. We observed abundant tunneling nanotubes (TNTs) connecting BMVECs and pericytes, and α-syn PFF transmitted through these TNTs. Furthermore, α-syn PFF accumulation in BMVECs did not promote TNT formation, but activated the molecular motor Myo1d. Inhibition of Myo1d prevented α-syn PFF transfer from BMVECs to pericytes and decreased the colocalization of Myo1d and F-actin in BMVECs. In summary, we are the first to demonstrate that α-syn PFF spread from BMVECs to pericytes through a mechanism involving TNTs and myosin. Targeting Myo1d may be a promising approach to prevent α-syn spreading from the blood to the brain.

Keywords: Cellular neuroscience; Molecular neuroscience; Neuroscience; Omics; Transcriptomics.