@article{4bc166fb9a9842ed9020662e7d731621,
title = "Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice",
abstract = "Aggregation of misfolded α-synuclein (α-syn) is the major component of Lewy bodies and neurites in Parkinson{\textquoteright}s disease (PD) and related α-synucleinopathies. Some α-syn mutations (e.g., A53T) in familial PD recapitulate the α-syn pathology in transgenic mice, which supports the importance of pathologic α-syn in driving the pathogenesis of α-synucleinopathies. Lymphocyte activation gene 3 (Lag3) is a receptor of α-syn fibrils facilitating pathologic α-syn spread; however, the role of Lag3 in mediating the pathogenesis in α-syn transgenic mice is not clear. Here, we report that depletion of Lag3 in human α-syn A53T transgenic (hA53T) mice significantly reduces the level of detergent-insoluble α-syn aggregates and phosphorylated ser129 α-syn, and inhibits activation of microglia and astrocytes. The absence of Lag3 significantly delays disease progression and reduces the behavioral deficits in hA53T transgenic mice leading to prolonged survival. Taken together, these results show that Lag3 contributes to the pathogenesis in the α-syn A53T transgenic mouse model.",
keywords = "Lag3, Parkinson{\textquoteright} disease, aggregation, α-synuclein, α-synucleinopathy",
author = "Hao Gu and Xiuli Yang and Xiaobo Mao and Enquan Xu and Chen Qi and Haibo Wang and Saurav Brahmachari and Bethany York and Manjari Sriparna and Amanda Li and Michael Chang and Pavan Patel and Dawson, {Valina L.} and Dawson, {Ted M.}",
note = "Funding Information: This work was supported by NIH R01 NS107318 and NIH K01 AG056841, American Parkinson{\textquoteright}s Disease Association, Parkinson{\textquoteright}s Foundation the Stanley Fahn Junior Faculty Award PF-JFA-1933, Maryland Stem Cell Research Foundation Discovery Award 2019-MSCRFD-4292, and the JPB Foundation. TD is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases. Funding Information: We acknowledge the join participation by the Adrienne Helis Malvin Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjugation with the Johns Hopkins Hospital and the Johns Hopkins University School of Medicine and the Foundation{\textquoteright}s Parkinson{\textquoteright}s Disease Program M-2014. Funding. This work was supported by NIH R01 NS107318 and NIH K01 AG056841, American Parkinson{\textquoteright}s Disease Association, Parkinson{\textquoteright}s Foundation the Stanley Fahn Junior Faculty Award PF-JFA-1933, Maryland Stem Cell Research Foundation Discovery Award 2019-MSCRFD-4292, and the JPB Foundation. TD is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Gu, Yang, Mao, Xu, Qi, Wang, Brahmachari, York, Sriparna, Li, Chang, Patel, Dawson and Dawson.",
year = "2021",
month = mar,
day = "10",
doi = "10.3389/fncel.2021.656426",
language = "English (US)",
volume = "15",
journal = "Frontiers in Cellular Neuroscience",
issn = "1662-5102",
publisher = "Frontiers Research Foundation",
}