Transgenic Overexpression of GPNMB Protects Against MPTP-Induced Neurodegeneration

被引:28
|
作者
Budge, Kevin M. [1 ,2 ]
Neal, Matthew L. [3 ,4 ]
Richardson, Jason R. [3 ,4 ]
Safadi, Fayez F. [1 ,2 ,5 ]
机构
[1] Kent State Univ, Sch Biomed Sci, Kent, OH 44242 USA
[2] Northeast Ohio Med Univ, Dept Anat & Neurobiol, Rootstown, OH 44272 USA
[3] Northeast Ohio Med Univ, Dept Pharmaceut Sci, Rootstown, OH 44272 USA
[4] Florida Int Univ, Robert Stempel Sch Publ Hlth & Social Work, Dept Environm Hlth Sci, Miami, FL 33199 USA
[5] Akron Childrens Hosp, Rebecca D Considine Res Inst, Akron, OH 44308 USA
基金
美国国家卫生研究院;
关键词
Parkinson's disease; GPNMB; Neuroprotective; MPTP; Neuroinflammation; Microglia; AMYOTROPHIC-LATERAL-SCLEROSIS; PARKINSONS-DISEASE; MICROGLIAL ACTIVATION; DOPAMINERGIC-NEURONS; MOUSE MODEL; B GPNMB; INFLAMMASOME ACTIVATION; ENHANCES BONE; NITRIC-OXIDE; FACTOR-ALPHA;
D O I
10.1007/s12035-020-01921-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Parkinson's disease (PD) is a progressive neurodegenerative disease highlighted by a marked loss of dopaminergic cell loss and motor disturbances. Currently, there are no drugs that slow the progression of the disease. A myriad of factors have been implicated in the pathogenesis and progression of PD including neuroinflammation. Although anti-inflammatory agents are being evaluated as potential disease-modifying therapies for PD, none has proven effective to date, suggesting that new and novel targets are needed. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that has recently been shown to reduce inflammation in astrocytes and to be increased in post-mortem PD brain samples. Here we show that transgenic overexpression of GPNMB protects against dopaminergic neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropridine mouse model of Parkinson's disease. Furthermore, GPNMB overexpression reduces gliosis and prevented microglial morphological changes following MPTP treatment compared with wild-type MPTP-treated mice. Additionally, recombinant GPNMB attenuates LPS-induced inflammation in primary mouse microglia. These results suggest a neuroprotective and anti-inflammatory role for GPNMB and warrant further investigation for GPNMB as a novel therapy for PD.
引用
收藏
页码:2920 / 2933
页数:14
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