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- Title
Pael-R transgenic mice crossed with parkin deficient mice displayed progressive and selective catecholaminergic neuronal loss.
- Authors
Hua-Qin Wang; Imai, Yuzuru; Inoue, Haruhisa; Kataoka, Ayane; Iita, Sachiko; Nukina, Nobuyuki; Takahashi, Ryosuke
- Abstract
Parkin, a ubiquitin ligase, is responsible for autosomal recessive juvenile parkinsonism (AR-JP). We identified parkin-associated endothelin receptor-like receptor (Pael-R) as a substrate of parkin, whose accumulation is thought to induce unfolded protein response (UPR) -mediated cell death, leading to dopaminergic neurodegeneration. To create an animal model of AR-JP, we generated parkin knockout/Pael-R transgenic ( parkin-ko/ Pael-R-tg) mice. parkin-ko/ Pael-R-tg mice exhibited early and progressive loss of dopaminergic as well as noradrenergic neurons without formation of inclusion bodies, recapitulating the pathological features of AR-JP. Evidence of activation of UPR and up-regulation of dopamine and its metabolites were observed throughout the lifetime. Moreover, complex I activity of mitochondria isolated from parkin-ko/ Pael-R-tg mice was significantly reduced later in life. These findings suggest that persistent induction of unfolded protein stress underlies chronic progressive catecholaminergic neuronal death, and that dysfunction of mitochondrial complex I and oxidative stress might be involved in the progression of Parkinson’s disease. parkin-ko/ Pael-R-tg mice represents an AR-JP mouse model displaying chronic and selective loss of catecholaminergic neurons.
- Subjects
UBIQUITIN; LIGASES; PARKINSON'S disease; NEURONS; NEUROCHEMISTRY
- Publication
Journal of Neurochemistry, 2008, Vol 107, Issue 1, p171
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2008.05607.x