Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo
Dynamins
Male
Mice, Knockout
Neuroscience and Neurobiology
Dopamine
Dopaminergic Neurons
Parkinson Disease
Mitochondrial Dynamics
Article
3. Good health
Mice, Inbred C57BL
Mitochondrial Proteins
Disease Models, Animal
HEK293 Cells
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Humans
Protein Kinases
DOI:
10.1038/ncomms6244
Publication Date:
2014-11-05T13:13:03Z
AUTHORS (9)
ABSTRACT
AbstractMitochondrial 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 and fusion has considerable potential for treating human diseases. To determine the therapeutic impact of targeting these pathways on PD, we used two complementary mouse models of mitochondrial impairments as seen in PD. We show here that blocking mitochondrial fission is neuroprotective in the PTEN-induced putative kinase-1 deletion (PINK1−/−) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse models. Specifically, we show that inhibition of the mitochondrial fission GTPase dynamin-related protein-1 (Drp1) using gene-based and small-molecule approaches attenuates neurotoxicity and restores pre-existing striatal dopamine release deficits in these animal models. These results suggest Drp1 inhibition as a potential treatment for PD.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (70)
CITATIONS (192)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....