Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo

• DOI: 10.1038/ncomms6244
• Publication Date: 2014-11-05T13:13:03Z
• Authors: Phillip M. Rappold; Mei Cui; Jonathan C. Grima; Rebecca Z. Fan; Karen L. de Mesy-...; Linan Chen; Xiaoxi Zhuang; William J. Bowers; Kim Tieu
• Keywords: DNM1L; Neurotoxicity; PINK1; MPTP

Mitochondrial dysfunction has been reported in both familial and sporadic Parkinson's disease (PD). However, effective therapy targeting this pathway is currently inadequate. Recent studies suggest that manipulating the processes of mitochondrial fission fusion considerable potential for treating human diseases. To determine therapeutic impact these pathways on PD, we used two complementary mouse models impairments as seen PD. We show here blocking neuroprotective PTEN-induced putative kinase-1 deletion (PINK1(-/-)) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine models. Specifically, inhibition GTPase dynamin-related protein-1 (Drp1) using gene-based small-molecule approaches attenuates neurotoxicity restores pre-existing striatal dopamine release deficits animal These results Drp1 a treatment