Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice.
Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice.
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淋巴细胞激活基因3（Lag 3）在α-突触核蛋白转基因小鼠中参与α-突触核蛋白病
DOI：
10.3389/fncel.2021.656426
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发表时间：
2021
影响因子：
5.3
通讯作者：
Dawson TM
中科院分区：
文献类型：
--
作者：
Gu H;Yang X;Mao X;Xu E;Qi C;Wang H;Brahmachari S;York B;Sriparna M;Li A;Chang M;Patel P;Dawson VL;Dawson TM
错误折叠的α-突触核蛋白（α-syn）聚集是帕金森病（PD）及相关α-突触核蛋白病中路易体和神经突起的主要成分。一些α-syn突变（例如，A53 T）在家族性PD中的表达，概括了转基因小鼠中的α-syn病理学，这支持了病理性α-syn在驱动α-synucleinopathies发病机制中的重要性。淋巴细胞活化基因3（Lymphocyte activation gene 3，Lag 3）是α-syn原纤维的受体，可促进病理性α-syn扩散;然而，Lag 3在α-syn转基因小鼠中介导发病机制的作用尚不清楚。在这里，我们报告了人α-syn A53 T转基因（hA 53 T）小鼠中Lag 3的消耗显著降低了洗涤剂不溶性α-syn聚集体和磷酸化ser 129 α-syn的水平，并抑制了小胶质细胞和星形胶质细胞的活化。Lag 3的缺失显著延迟了疾病进展，并减少了hA 53 T转基因小鼠的行为缺陷，从而延长了存活时间。总之，这些结果表明，Lag 3有助于α-syn A53 T转基因小鼠模型中的发病机制。
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.
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影响因子：
16.2
作者：
Giasson, BI;Duda, JE;Lee, VMY
通讯作者：
Lee, VMY
DOI：
10.1126/science.aat8407
发表时间：
2018-11-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kam TI;Mao X;Park H;Chou SC;Karuppagounder SS;Umanah GE;Yun SP;Brahmachari S;Panicker N;Chen R;Andrabi SA;Qi C;Poirier GG;Pletnikova O;Troncoso JC;Bekris LM;Leverenz JB;Pantelyat A;Ko HS;Rosenthal LS;Dawson TM;Dawson VL
通讯作者：
Dawson VL
影响因子：
16.2
作者：
Linnerbauer M;Wheeler MA;Quintana FJ
通讯作者：
Quintana FJ
影响因子：
16.6
作者：
Choi, Insup;Zhang, Yuanxi;Yue, Zhenyu
通讯作者：
Yue, Zhenyu
DOI：
10.1126/science.aah3374
发表时间：
2016-09-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mao X;Ou MT;Karuppagounder SS;Kam TI;Yin X;Xiong Y;Ge P;Umanah GE;Brahmachari S;Shin JH;Kang HC;Zhang J;Xu J;Chen R;Park H;Andrabi SA;Kang SU;Gonçalves RA;Liang Y;Zhang S;Qi C;Lam S;Keiler JA;Tyson J;Kim D;Panicker N;Yun SP;Workman CJ;Vignali DA;Dawson VL;Ko HS;Dawson TM
通讯作者：
Dawson TM