| First Author | Martin LJ | Year | 2014 |
| Journal | Neurobiol Aging | Volume | 35 |
| Issue | 5 | Pages | 1132-52 |
| PubMed ID | 24325796 | Mgi Jnum | J:212732 |
| Mgi Id | MGI:5582032 | Doi | 10.1016/j.neurobiolaging.2013.11.008 |
| Citation | Martin LJ, et al. (2014) The mitochondrial permeability transition pore regulates Parkinson's disease development in mutant alpha-synuclein transgenic mice. Neurobiol Aging 35(5):1132-52 |
| abstractText | Parkinson's disease (PD) is a movement disorder caused by neurodegeneration in neocortex, substantia nigra and brainstem, and synucleinopathy. Some inherited PD is caused by mutations in alpha-synuclein (alphaSyn), and inherited and idiopathic PD is associated with mitochondrial perturbations. However, the mechanisms of pathogenesis are unresolved. We characterized a human alphaSyn transgenic mouse model and tested the hypothesis that the mitochondrial permeability transition pore (mPTP) is involved in the disease mechanisms. C57BL/6 mice expressing human A53T-mutant alphaSyn driven by a thymic antigen-1 promoter develop a severe, age-related, fatal movement disorder involving ataxia, rigidity, and postural instability. These mice develop synucleinopathy and neocortical, substantia nigra, and cerebello-rubro-thalamic degeneration involving mitochondriopathy and apoptotic and non-apoptotic neurodegeneration. Interneurons undergo apoptotic degeneration in young mice. Mutant alphaSyn associated with dysmorphic neuronal mitochondria and bound voltage-dependent anion channels. Genetic ablation of cyclophilin D, an mPTP modulator, delayed disease onset, and extended lifespans of mutant alphaSyn mice. Thus, mutant alphaSyn transgenic mice on a C57BL/6 background develop PD-like phenotypes, and the mPTP is involved in their disease mechanisms. |
