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Glycoprotein NMB: an Emerging Role in Neurodegenerative Disease

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Abstract

Neurodegeneration is characterized by severe neuronal loss leading to the cognitive and physical impairments that define various neurodegenerative diseases. Neuroinflammation is one hallmark of neurodegenerative diseases and can ultimately contribute to disease progression. Increased inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1 β), and tumor necrosis factor-α (TNF-α) are associated with Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Unfortunately, current therapeutic options lack ability to stop or effectively slow progression of these diseases and are primarily aimed at alleviating symptoms. Thus, it is crucial to discover novel treatment candidates for neurodegenerative diseases. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type-I transmembrane glycoprotein first identified in a melanoma cell line. GPNMB augments bone mineral deposition by stimulating osteoblast differentiation. Aside from its anabolic function in the bone, emerging evidence suggests that GPNMB has anti-inflammatory and reparative functions. GPNMB has also been demonstrated to be neuroprotective in an animal model of ALS, cerebral ischemia, and other disease models. Given these discoveries, GPNMB should be investigated as a potential therapeutic option for multiple neurodegenerative diseases.

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Acknowledgments

The writing of this review was supported in part by grants from the NIH (RO1ES021800) and the Michael J Fox Foundation for Parkinson’s Disease Research to JRR. Additional support was provided through generous donations from the Glenn and Karen Leppo, the Richard Nicely, and the Allan and Janice Woll Parkinson’s Research Funds. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of NIH or any other funding source.

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Correspondence to Fayez F. Safadi.

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Budge, K.M., Neal, M.L., Richardson, J.R. et al. Glycoprotein NMB: an Emerging Role in Neurodegenerative Disease. Mol Neurobiol 55, 5167–5176 (2018). https://doi.org/10.1007/s12035-017-0707-z

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