| Abstract: | ![]()
AIM：To investigate the neuroprotective effects of vasonatrin peptide (VNP) on the injury of dopaminergic neurons induced by 1-methyl-4-phenylpyridinium (MPP+). METHODS：Cultured dopaminergic neurons from the mouse ventral mesencephalon were exposed to MPP+, and the effects of VNP on the neurotoxicity of MPP+ were eva-luated by cell viability analysis and immunofluorescence staining. Various kinds of agonists and antagonists were used to clarify the mechanism underlying the effects of VNP. RESULTS：MPP+ caused injuries in the dopaminergic neurons. VNP significantly increased the viability, axon number and axon length of the dopaminergic neurons. The MPP+-induced depolymerization of β-tubulin Ⅲ was also attenuated by the treatment with VNP. In addition, VNP significantly increased the intracellular levels of cGMP. These effects of VNP were mimicked by 8-Br-cGMP (a cell-permeable analog of cGMP), whereas inhibited by HS-142-1 ［the antagonist of the particulate guanylyl cyclase-coupled natriuretic peptide receptors (NPR)］, or KT-5823 ［a cGMP-dependent protein kinase (PKG) inhibitor］. CONCLUSION：VNP attenuates the neurotoxicity of MPP+ via guanylyl cyclase-coupled NPR/cGMP/PKG pathway, indicating that VNP might be a new effective reagent in the treatment of neural degeneration of dopaminergic neurons in Parkinson disease. |
