| Autor: |
Mao, Xiaobo, Gu, Hao, Kim, Donghoon, Kimura, Yasuyoshi, Wang, Ning, Xu, Enquan, Kumbhar, Ramhari, Ming, Xiaotian, Wang, Haibo, Chen, Chan, Zhang, Shengnan, Jia, Chunyu, Liu, Yuqing, Bian, Hetao, Karuppagounder, Senthilkumar S., Akkentli, Fatih, Chen, Qi, Jia, Longgang, Hwang, Heehong, Lee, Su Hyun |
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| Zdroj: |
Nature Communications; 7/30/2024, Vol. 15 Issue 1, p1-19, 19p |
| Abstrakt: |
Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of α-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by α-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for α-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologic α-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson's disease and related α-synucleinopathies. Pathologic α-synuclein spreads from cell-to-cell through binding to the lymphocyteactivation gene 3 (Lag3). Here, the authors demonstrate that the amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 and facilitates the binding, internalization, transmission, and toxicity of pathologic α-synuclein. [ABSTRACT FROM AUTHOR] |
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Complementary Index |
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