| http://purl.uniprot.org/citations/27960106 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27960106 | http://www.w3.org/2000/01/rdf-schema#comment | "Fungicide exposure causes degeneration of dopaminergic neurons and contributes to Parkinson's disease (PD). Benomyl inhibits enzymes responsible for detoxifying the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde. Aldose reductase (AR) is known as tetrahydrobiopterin (BH4) reductase that generates BH4, a cofactor for tyrosine hydroxylase (TH) involved in dopamine synthesis. AR also acts as an aldehyde reductase involved in detoxifying 3,4-dihydroxyphenylacetaldehyde. In PD patients, the level of AR is significantly lower in the cerebellum. To determine if AR deficiency contributes to PD, AR wild-type (AR+/+) and knockout (AR-/-) mice were administrated with 1-methyl-4-phenyl -1,2,3,6-tetrahydropyridine (MPTP). The MPTP-treated AR-/- mice showed more severe behavioral deficits and brain damage than that of AR+/+ mice. Contrary to expectation, under normal or MPTP-treated condition, AR-/- mice showed a significant elevation of BH4 and dopamine in the midbrain, suggesting that either AR does not contribute to BH4 production, or other BH4 synthetic pathways are induced. The AR-/- brain showed upregulation of peroxynitrite, inducible nitric oxide synthase and downregulation of antioxidant enzymes, Cu/Zn superoxide dismutase (SOD) and peroxiredoxin 2 (Prx2), which indicate an increase in oxidative stress. In line with the animal data, pretreating the SH-SY5Y cells with AR inhibitors (Fidarestat or Epalrestat) before MPP+ treatment, increased severe cell death and mitochondrial fragmentation with downregulation of SOD were observed when compared to the MPP+ treatment alone. Cycloxygenase 2 (COX2), which can lead to the oxidation of dopamine, was upregulated in AR-/- brains. Autophagic proteins, beclin-1 and LC3B were also downregulated. The loss of dopaminergic neurons was associated with activation of p-ERK1/2. These findings suggest that AR plays an important role in protecting dopaminergic neuron against neurotoxic metabolites in PD."xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.neurobiolaging.2016.11.008"xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/author | "Zhang X."xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/author | "Hwang O."xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/author | "Chung S.S.M."xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/author | "Chung S.K."xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/author | "Son H.J."xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/author | "Lai A.K.W."xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/author | "Yeung P.K.K."xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/name | "Neurobiol Aging"xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/pages | "119-133"xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/title | "Aldose reductase deficiency leads to oxidative stress-induced dopaminergic neuronal loss and autophagic abnormality in an animal model of Parkinson's disease."xsd:string |
| http://purl.uniprot.org/citations/27960106 | http://purl.uniprot.org/core/volume | "50"xsd:string |
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