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Int J Biol Sci 2013; 9(2):149-155. doi:10.7150/ijbs.5617

Research Paper

Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity

Fangfang Bi1, Fang Li1, Cao Huang2, Hongxia Zhou1,✉

1. Department of Neurology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA
2. Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA

Abstract

Parkinson's disease primarily results from progressive degeneration of dopaminergic neurons in the substantia nigra. Both neuronal toxicants and genetic factors are suggested to be involved in the disease pathogenesis. The mitochondrial toxicant 1-methyl-4-phenylpyridinium (MPP+) shows a highly selective toxicity to dopaminergic neurons. Recent studies indicate that mutation in the vacuolar protein sorting 35 (vps35) gene segregates with Parkinson's disease in some families, but how mutation in the vps35 gene causes dopaminergic cell death is not known. Here, we report that enhanced VPS35 expression protected dopaminergic cells against MPP+ toxicity and that this neuroprotection was compromised by pathogenic mutation in the gene. A loss of neuroprotective functions contributes to the pathogenesis of VPS35 mutation in Parkinson's disease.

Keywords: Parkinson's disease, vacuolar protein sorting 35, VPS35, 1-methyl-4-phenylpyridinium, MPP+.

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How to cite this article:
Bi F, Li F, Huang C, Zhou H. Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity. Int J Biol Sci 2013; 9(2):149-155. doi:10.7150/ijbs.5617. Available from http://www.ijbs.com/v09p0149.htm