| Title | Aldose reductase deficiency leads to oxidative stress-induced dopaminergic neuronal loss and autophagic abnormality in an animal model of Parkinson's disease |
| Creator | |
| Date Issued | 2017-02-01 |
| Source Publication | Neurobiology of Aging
 |
| ISSN | 0197-4580 |
| Volume | 50Pages:119-133 |
| Abstract | 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 (BH) reductase that generates BH, 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 BH and dopamine in the midbrain, suggesting that either AR does not contribute to BH production, or other BH 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. |
| Keyword | Aldose reductase Knockout mice Oxidative stress Parkinson's disease |
| DOI | 10.1016/j.neurobiolaging.2016.11.008 |
| URL | View source |
| Language | 英语English |
| Scopus ID | 2-s2.0-85002665130 |
| Citation statistics | |
| Document Type | Journal article |
| Identifier | http://repository.uic.edu.cn/handle/39GCC9TT/6370 |
| Collection | Beijing Normal-Hong Kong Baptist University |
| Corresponding Author | Chung，Sookja K. |
| Affiliation | 1.School of Biomedical Sciences,The University of Hong Kong,Hong Kong SAR,Hong Kong 2.Department of Biochemistry,University of Ulsan College of Medicine,Seoul,South Korea 3.Division of Science and Technology,United International College,Zhuhai,China 4.Research Center of Heart,Brain,Hormone and Healthy Aging,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong SAR,China |
| Recommended Citation GB/T 7714 | Yeung，Patrick K.K.,Lai，Angela K.W.,Son，Hyo Jinet al. Aldose reductase deficiency leads to oxidative stress-induced dopaminergic neuronal loss and autophagic abnormality in an animal model of Parkinson's disease[J]. Neurobiology of Aging, 2017, 50: 119-133. |
| APA | Yeung，Patrick K.K., Lai，Angela K.W., Son，Hyo Jin., Zhang，Xu., Hwang，Onyou., .. & Chung，Sookja K. (2017). Aldose reductase deficiency leads to oxidative stress-induced dopaminergic neuronal loss and autophagic abnormality in an animal model of Parkinson's disease. Neurobiology of Aging, 50, 119-133. |
| MLA | Yeung，Patrick K.K.,et al."Aldose reductase deficiency leads to oxidative stress-induced dopaminergic neuronal loss and autophagic abnormality in an animal model of Parkinson's disease". Neurobiology of Aging 50(2017): 119-133. |
| Files in This Item: | There are no files associated with this item. | |||||
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
BNBU 
Library
Edit Comment