Frontiers in Cellular Neuroscience (Mar 2021)
Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice
- Hao Gu,
- Hao Gu,
- Xiuli Yang,
- Xiuli Yang,
- Xiaobo Mao,
- Xiaobo Mao,
- Enquan Xu,
- Enquan Xu,
- Chen Qi,
- Chen Qi,
- Haibo Wang,
- Haibo Wang,
- Saurav Brahmachari,
- Saurav Brahmachari,
- Bethany York,
- Bethany York,
- Manjari Sriparna,
- Manjari Sriparna,
- Amanda Li,
- Amanda Li,
- Michael Chang,
- Michael Chang,
- Pavan Patel,
- Pavan Patel,
- Valina L. Dawson,
- Valina L. Dawson,
- Valina L. Dawson,
- Valina L. Dawson,
- Valina L. Dawson,
- Ted M. Dawson,
- Ted M. Dawson,
- Ted M. Dawson,
- Ted M. Dawson,
- Ted M. Dawson
Affiliations
- Hao Gu
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Hao Gu
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Xiuli Yang
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Xiuli Yang
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Xiaobo Mao
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Xiaobo Mao
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Enquan Xu
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Enquan Xu
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Chen Qi
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Chen Qi
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Haibo Wang
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Haibo Wang
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Saurav Brahmachari
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Saurav Brahmachari
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Bethany York
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Bethany York
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Manjari Sriparna
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Manjari Sriparna
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Amanda Li
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Amanda Li
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Michael Chang
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Michael Chang
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Pavan Patel
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Pavan Patel
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Valina L. Dawson
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Valina L. Dawson
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Valina L. Dawson
- Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, United States
- Valina L. Dawson
- Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Valina L. Dawson
- Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Ted M. Dawson
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Ted M. Dawson
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Ted M. Dawson
- Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, United States
- Ted M. Dawson
- Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Ted M. Dawson
- Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- DOI
- https://doi.org/10.3389/fncel.2021.656426
- Journal volume & issue
-
Vol. 15
Abstract
Aggregation of misfolded α-synuclein (α-syn) is the major component of Lewy bodies and neurites in Parkinson’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
