| First Author | Budge KM | Year | 2020 |
| Journal | Mol Neurobiol | Volume | 57 |
| Issue | 7 | Pages | 2920-2933 |
| PubMed ID | 32436108 | Mgi Jnum | J:326337 |
| Mgi Id | MGI:6863751 | Doi | 10.1007/s12035-020-01921-6 |
| Citation | Budge KM, et al. (2020) Transgenic Overexpression of GPNMB Protects Against MPTP-Induced Neurodegeneration. Mol Neurobiol 57(7):2920-2933 |
| abstractText | 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. |
