Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice

Hao Gu, Xiuli Yang, Xiaobo Mao, Enquan Xu, Chen Qi, Haibo Wang, Saurav Brahmachari, Bethany York, Manjari Sriparna, Amanda Li, Michael Chang, Pavan Patel, Valina L. Dawson, Ted M. Dawson

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number656426
JournalFrontiers in Cellular Neuroscience
StatePublished - Mar 10 2021


  • Lag3
  • Parkinson’ disease
  • aggregation
  • α-synuclein
  • α-synucleinopathy

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice'. Together they form a unique fingerprint.

Cite this