1. Pael receptor is involved in dopamine metabolism in the nigrostriatal system
- Author
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Mariko Soda, Shosuke Ito, Tohru Kodama, Toshihiko Aosaki, Tatsu Fuwa, Shigeyoshi Itohara, Kazumasa Wakamatsu, Masao Masuda, Wang Hua-Qin, Ryosuke Takahashi, Haruhisa Inoue, Ayane Kataoka, Sadayuki Matsumoto, Toshio Ikeda, Yoshiko Honda, Masami Miura, Satoshi Kaneko, Yuzuru Imai, and Kayoko Tsukita
- Subjects
Male ,medicine.medical_specialty ,Parkinson's disease ,Dopamine ,Ubiquitin-Protein Ligases ,Neurotoxins ,Drug Resistance ,Mice, Transgenic ,Substantia nigra ,Striatum ,Biology ,Parkin ,Receptors, G-Protein-Coupled ,Mice ,chemistry.chemical_compound ,Parkinsonian Disorders ,Internal medicine ,Neural Pathways ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Oxidopamine ,Mice, Knockout ,General Neuroscience ,Endoplasmic reticulum ,MPTP ,Dopaminergic ,General Medicine ,medicine.disease ,Corpus Striatum ,Ubiquitin ligase ,Substantia Nigra ,Endocrinology ,nervous system ,chemistry ,1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ,biology.protein ,3,4-Dihydroxyphenylacetic Acid - Abstract
Pael receptor (Pael-R) has been identified as one of the substrates of Parkin, a ubiquitin ligase responsible for autosomal recessive juvenile Parkinsonism (AR-JP). When Parkin is inactivated, unfolded Pael-R accumulates in the endoplasmic reticulum and results in neuronal death by unfolded protein stress, suggesting that Pael-R has an important role in the pathogenesis of AR-JP. Here we report the analyses on Pael-R-deficient (KO) and Pael-R-transgenic (Tg) mice. The striatal dopamine (DA) level of Pael-R KO mice was only 60% of that in normal mice, while in Pael-R Tg mice, striatal 3,4-dihydroxyphenylacetic acid (DOPAC) as well as vesicular DA content increased. Moreover, the nigrostriatal dopaminergic neurons of Pael-R Tg mice are more vulnerable to Parkinson's disease-related neurotoxins while those of Pael-R KO mice are less. These results strongly suggest that the Pael-R signal regulates the amount of DA in the dopaminergic neurons and that excessive Pael-R expression renders dopaminergic neurons susceptible to chronic DA toxicity.
- Published
- 2007
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