Deficiency of miR-29b2/c leads to accelerated aging and neuroprotection in MPTP-induced Parkinson's disease mice.
Deficiency of miR-29b2/c leads to accelerated aging and neuroprotection in MPTP-induced Parkinson's disease mice.
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DOI：
10.18632/aging.203545
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发表时间：
2021-09-20
期刊：
影响因子：
--
通讯作者：
Huang F
中科院分区：
文献类型：
--
作者：
Bai X;Zhang X;Fang R;Wang J;Ma Y;Liu Z;Dong H;Li Q;Ge J;Yu M;Fei J;Sun R;Huang F
研究揭示了miR-29在衰老和帕金森病（PD）中的联系。在此，我们发现1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的PD小鼠血清中miR-29的水平呈现动态变化。利用miR-29 b2/c基因敲除小鼠（miR-29 b2/c KO）研究miR-29 b2/c在衰老和PD中的作用。与野生型（WT）小鼠相比，miR-29 b2/c KO小鼠的特征为体重明显减轻、脊柱后凸、肌无力和步态异常。WT还出现了明显的真皮增厚和脂肪组织减少。然而，miR-29 b2/c的缺乏减轻了MPTP诱导的多巴胺能系统的损伤和黑质纹状体通路中的胶质细胞活化，从而改善了MPTP处理的KO小鼠的运动功能。miR-29 b2/c的敲除抑制了1-甲基-4-苯基吡啶鎓（MPP+）处理的混合胶质细胞、原代星形胶质细胞或LPS处理的原代小胶质细胞的原代培养物中炎性因子的表达。此外，miR-29 b2/c缺陷可增强AMPK活性，但抑制NF-κB p65信号转导。我们的研究结果表明，miR-29 b2/c KO小鼠表现出早衰样表型。在miR-29 b2/c基因敲除小鼠中，较少活化的胶质细胞和抑制的神经炎症可能产生多巴胺能神经保护作用。总之，miR-29 b2/c参与了衰老的调节，并在帕金森病中起着有害的作用。
Studies reveal a linkage of miR-29s in aging and Parkinson’s disease (PD). Here we show that the serum levels of miR-29s in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice exhibited dynamic changes. The role of miR-29b2/c in aging and PD was studied utilizing miR-29b2/c gene knockout mice (miR-29b2/c KO). miR-29b2/c KO mice were characterized by a markedly lighter weight, kyphosis, muscle weakness and abnormal gait, when compared with wild-type (WT) mice. The WT also developed apparent dermis thickening and adipose tissue reduction. However, deficiency of miR-29b2/c alleviated MPTP-induced damages of the dopaminergic system and glial activation in the nigrostriatal pathway and consequently improved the motor function of MPTP-treated KO mice. Knockout of miR-29b2/c inhibited the expression of inflammatory factors in 1-methyl-4-phenylpyridinium (MPP+)-treated primary cultures of mixed glia, primary astrocytes, or LPS-treated primary microglia. Moreover, miR-29b2/c deficiency enhanced the activity of AMPK but repressed the NF-κB p65 signaling in glial cells. Our results show that miR-29b2/c KO mice display the progeria-like phenotype. Less activated glial cells and repressed neuroinflammation might bring forth dopaminergic neuroprotection in miR-29b2/c KO mice. Conclusively, miR-29b2/c is involved in the regulation of aging and plays a detrimental role in Parkinson’s disease.
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DOI：
10.1002/mds.27037
发表时间：
2017-07
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Collier TJ;Kanaan NM;Kordower JH
通讯作者：
Kordower JH
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
帕金森病患者血清microRNA 29家族的下调
影响因子：
4.6
作者：
Bai X;Tang Y;Yu M;Wu L;Liu F;Ni J;Wang Z;Wang J;Fei J;Wang W;Huang F;Wang J
通讯作者：
Wang J
影响因子：
6.3
作者：
Khanna, Savita;Rink, Cameron;Sen, Chandan K.
通讯作者：
Sen, Chandan K.
影响因子：
--
作者：
Dooley J;Lagou V;Garcia-Perez JE;Himmelreich U;Liston A
通讯作者：
Liston A