carboxypiperazinyl-propylphosphonic-acid and Disease-Models--Animal

The uncoupling protein 4 (ucp-4) gene is involved in age-dependent neurodegeneration in C. elegans. Therefore, we aimed to investigate the mechanism underlying the association between mitochondrial uncoupling and neurodegeneration by examining the effects of uncoupling agents and ucp-4 overexpression in C. elegans. Treatment with either DNP or CCCP improved neuronal defects in wild type during aging. Uncoupling agents also restored neuronal phenotypes of ucp-4 mutants to those exhibited by wild type, while ucp-4 overexpression attenuated the severity of age-dependent neurodegeneration. Neuronal improvements were further associated with reductions in mitochondrial membrane potentials. However, these age-dependent neuroprotective effects were limited in mitophagy-deficient mutant, pink-1, background. These results suggest that membrane uncoupling can attenuate age-dependent neurodegeneration by stimulating mitophagy.

Topics: 2,4-Dinitrophenol; Aging; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Disease Models, Animal; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Uncoupling Proteins; Mitophagy; Mutation; Neurodegenerative Diseases; Organophosphonates; Piperazines