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23 October 2017

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Int J Med Sci 2008; 5(2):92-99. doi:10.7150/ijms.5.92

Research Paper

Vgf is a novel biomarker associated with muscle weakness in amyotrophic lateral sclerosis (ALS), with a potential role in disease pathogenesis

Zhong Zhao1,2, Dale J. Lange1,3, Lap Ho1,2, Sara Bonini1,2, Belinda Shao1,2, Stephen R. Salton4,5, Sunil Thomas1,2, Giulio Maria Pasinetti1,2,4,5

1. James J. Peters Veterans Affairs Medical Center, Bronx, NY 10468
2. Departments of Psychiatry, Mount Sinai School of Medicine, New York, NY-10029
3. Departments of Neurology, Mount Sinai School of Medicine, New York, NY-10029
4. Departments of Neuroscience, Mount Sinai School of Medicine, New York, NY-10029
5. Departments of Geriatrics, Mount Sinai School of Medicine, New York, NY-10029

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Previous proteomic evidence revealed that the content of certain peptide fragments including Vgf-derived peptide aa 398-411 (Vgf398-411) of the precursor Vgf protein in the cerebral spinal fluid (CSF) correctly identified patients with ALS from normal and disease controls. Using quantitative ELISA immunoassay we found that the CSF levels of Vgf decreases with muscle weakness in patients with ALS. In SOD1 G93A transgenic mice, loss of full-length Vgf content in CSF, serum and in SMI-32 immunopositive spinal cord motor neurons is noted in asymptomatic animals (approximately 75 days old) and continues to show a progressive decline as animals weaken. In vitro studies show that viral-mediated exogenous Vgf expression in primary mixed spinal cord neuron cultures attenuates excitotoxic injury. Thus, while Vgf may be a reliable biomarker of progression of muscle weakness in patients with ALS, restoration of Vgf expression in spinal cord motor neurons may therapeutically rescue spinal cord motorneurons against excitotoxic injury.

Keywords: VGF, ALS, biomarker, excitotoxicity, SOD-1 mice, disease progression

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How to cite this article:
Zhao Z, Lange DJ, Ho L, Bonini S, Shao B, Salton SR, Thomas S, Pasinetti GM. Vgf is a novel biomarker associated with muscle weakness in amyotrophic lateral sclerosis (ALS), with a potential role in disease pathogenesis. Int J Med Sci 2008; 5(2):92-99. doi:10.7150/ijms.5.92. Available from http://www.medsci.org/v05p0092.htm