Mitochondrial inhibitor 3-nitroproprionic acid enhances oxidative modification of alpha-synuclein in a transgenic mouse model of multiple system atrophy-

Authors
K. Ubhi, P. Hyu Lee, A. Adame, C. Inglis, M. Mante et al.

Lab
University of California–San Diego, School of Medicine, Department of Neurosciences and Department of Pathology, La Jolla, California ; Yonsei University College of Medicine, Department of Neurology, Seoul, South Korea ; Innsbruck Medical University, Clin

Journal
Journal of Neuroscience Research

Abstract
Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by autonomic failure, parkinsonism, cerebellar ataxia, and oligodendrocytic accumulation of alpha-synuclein (_syn). Oxidative stress has been linked to neuronal death in MSA and the mitochondrial toxin 3-nitropropionic acid (3NP) is known to enhance the motor deficits and neurodegeneration in transgenic mice models of MSA. However, the effect of 3NP administration on _syn itself has not been studied. In this context, we examined the neuropathological effects of 3NP administration in _syn transgenic mice expressing human _syn (h_syn) under the control of the myelin basic protein (MBP) promoter and the effect of this administration on posttranslational modifications of _syn, on levels of total _syn, and on its solubility. We demonstrate that 3NP administration altered levels of nitrated and oxidized _syn in the MBP-h_syn tg while not affecting global levels of phosphorylated or total _syn. 3NP administration also exaggerated neurological deficits in the MBP-h_syn tg mice, resulting in widespread neuronal degeneration and behavioral impairment.

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)