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

作者：Qingrui Duan, Qingxi Zhang, Kun Nie, Rui Huang, J. Joshua Yang, Peikun He, Zihui Tie, Haifeng Huang, Guixian Ma, Yuhu Zhang, Yuyuan Gao, Lijuan Wang · 发表于：iScience · 年份：2023 · DOI：10.1016/j.isci.2023.107458 · 被引用次数：22 · 研究领域：Parkinson's Disease Mechanisms and Treatments、Neurological disorders and treatments、Botulinum Toxin and Related Neurological Disorders

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.