Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice
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 patholog...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-03-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2021.656426/full |
| id |
doaj-68d7804621e14b6ba09d1b75735fc7fb |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice Frontiers in Cellular Neuroscience Lag3 Parkinson’ disease α-synuclein α-synucleinopathy aggregation |
| author_facet |
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 |
| author_sort |
Hao Gu |
| title |
Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice |
| title_short |
Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice |
| title_full |
Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice |
| title_fullStr |
Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice |
| title_full_unstemmed |
Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice |
| title_sort |
lymphocyte activation gene 3 (lag3) contributes to α-synucleinopathy in α-synuclein transgenic mice |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Cellular Neuroscience |
| issn |
1662-5102 |
| publishDate |
2021-03-01 |
| description |
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. |
| topic |
Lag3 Parkinson’ disease α-synuclein α-synucleinopathy aggregation |
| url |
https://www.frontiersin.org/articles/10.3389/fncel.2021.656426/full |
| work_keys_str_mv |
AT haogu lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT haogu lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT xiuliyang lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT xiuliyang lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT xiaobomao lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT xiaobomao lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT enquanxu lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT enquanxu lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT chenqi lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT chenqi lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT haibowang lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT haibowang lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT sauravbrahmachari lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT sauravbrahmachari lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT bethanyyork lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT bethanyyork lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT manjarisriparna lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT manjarisriparna lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT amandali lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT amandali lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT michaelchang lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT michaelchang lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT pavanpatel lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT pavanpatel lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT valinaldawson lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT valinaldawson lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT valinaldawson lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT valinaldawson lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT valinaldawson lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT tedmdawson lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT tedmdawson lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT tedmdawson lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT tedmdawson lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice AT tedmdawson lymphocyteactivationgene3lag3contributestoasynucleinopathyinasynucleintransgenicmice |
| _version_ |
1724227038958583808 |
| spelling |
doaj-68d7804621e14b6ba09d1b75735fc7fb2021-03-10T04:40:14ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022021-03-011510.3389/fncel.2021.656426656426Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic MiceHao Gu0Hao Gu1Xiuli Yang2Xiuli Yang3Xiaobo Mao4Xiaobo Mao5Enquan Xu6Enquan Xu7Chen Qi8Chen Qi9Haibo Wang10Haibo Wang11Saurav Brahmachari12Saurav Brahmachari13Bethany York14Bethany York15Manjari Sriparna16Manjari Sriparna17Amanda Li18Amanda Li19Michael Chang20Michael Chang21Pavan Patel22Pavan Patel23Valina L. Dawson24Valina L. Dawson25Valina L. Dawson26Valina L. Dawson27Valina L. Dawson28Ted M. Dawson29Ted M. Dawson30Ted M. Dawson31Ted M. Dawson32Ted M. Dawson33Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesAdrienne Helis Malvin Medical Research Foundation, New Orleans, LA, United StatesDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesAdrienne Helis Malvin Medical Research Foundation, New Orleans, LA, United StatesDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesAggregation 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.https://www.frontiersin.org/articles/10.3389/fncel.2021.656426/fullLag3Parkinson’ diseaseα-synucleinα-synucleinopathyaggregation |