Aplp1 interacts with Lag3 to facilitate transmission of pathologicAlpha-synuclein

Authors
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, Ke, Xiyu, Chang, Michael, Li, Amanda, Yang, Jun, Rastegar, Cyrus, Sriparna, Manjari, Ge, Preston, Brahmachari, Saurav, Kim, Sangjune, Zhang, Shu, Shimoda, Yasushi, Saar, Martina, Liu, Haiqing, Kweon, Sin Ho, Ying, Mingyao, Workman, Creg J., Vignali, Dario A. A., Muller, Ulrike C., Liu, Cong, Ko, Han Seok, Dawson, Valina L., Dawson, Ted M.


Lab

Journal
Nature Communications

Abstract
PathologicAlpha-synuclein (Alpha-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid Beta precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologicAlpha-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced byAlpha-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization ofAlpha-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced byAlpha-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 forAlpha-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologicAlpha-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson's disease and relatedAlpha-synucleinopathies. PathologicAlpha-synuclein spreads from cell-to-cell through binding to the lymphocyteactivation gene 3 (Lag3). Here, the authors demonstrate that the amyloid Beta precursor-like protein 1 (Aplp1) interacts with Lag3 and facilitates the binding, internalization, transmission, and toxicity of pathologicAlpha-synuclein.

Keywords/Topics
interacts;facilitate;transmission;pathologic;synuclein;spreads;cell-to-cell;through;binding;lymphocyte-activation

BIOSEB Instruments Used:
Grip strength test (BIO-GS4)

Source :

https://www.nature.com/articles/s41467-024-49016-3

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