Targeting Caspase-3 as Dual Therapeutic Benefits by RNAi Facilitating Brain-Targeted Nanoparticles in a Rat Model of Parkinson's Disease

31Citations
Citations of this article
61Readers
Mendeley users who have this article in their library.

Abstract

The activation of caspase-3 is an important hallmark in Parkinson's disease. It could induce neuron death by apoptosis and microglia activation by inflammation. As a result, inhibition the activation of caspase-3 would exert synergistic dual effect in brain in order to prevent the progress of Parkinson's disease. Silencing caspase-3 genes by RNA interference could inhibit the activation of caspase-3. We developed a brain-targeted gene delivery system based on non-viral gene vector, dendrigraft poly-L-lysines. A rabies virus glycoprotein peptide with 29 amino-acid linked to dendrigraft poly-L-lysines could render gene vectors the ability to get across the blood brain barrier by specific receptor mediated transcytosis. The resultant brain-targeted vector was complexed with caspase-3 short hairpin RNA coding plasmid DNA, yielding nanoparticles. In vivo imaging analysis indicated the targeted nanoparticles could accumulate in brain more efficiently than non-targeted ones. A multiple dosing regimen by weekly intravenous administration of the nanoparticles could reduce activated casapse-3 levels, significantly improve locomotor activity and rescue dopaminergic neuronal loss and in Parkinson's disease rats' brain. These results indicated the rabies virus glycoprotein peptide modified brain-targeted nanoparticles were promising gene delivery system for RNA interference to achieve anti-apoptotic and anti-inflammation synergistic therapeutic effects by down-regulation the expression and activation of caspase-3. © 2013 Liu et al.

Cite

CITATION STYLE

APA

Liu, Y., Guo, Y., An, S., Kuang, Y., He, X., Ma, H., … Jiang, C. (2013). Targeting Caspase-3 as Dual Therapeutic Benefits by RNAi Facilitating Brain-Targeted Nanoparticles in a Rat Model of Parkinson’s Disease. PLoS ONE, 8(5). https://doi.org/10.1371/journal.pone.0062905

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free