The Role of NOX4 in Parkinson’s Disease with Dementia
Abstract
:1. Introduction
2. Results
2.1. Motor Deficit, Loss of TH+ Cells, Increased Expression of α-Synuclein and NOX1 in the 6-OHDA-Lesion Side of the Striatum and Substantia Nigra
2.2. Cognitive Deficit Induced by MFB Injury Caused by 6-OHDA Injection
2.3. Levels of Alpha-Synuclein and Amyloid Beta Pathology in Animals with MFB Injury Caused by 6-OHDA Injection
2.4. Increased Levels of Phosphorylated Alpha-Synuclein, Aggregated Amyloid Beta, and NADPH Oxidase-4 in the Hippocampus
2.5. Inhibition of NADPH Oxidase-4 in Hippocampal Neurons Reduced Cognitive Impairment in a PD Animal Model
2.6. NOX4 Knockdown Reduces 6-OHDA-Mediated Amyloid Beta and A11 Oligomer Upregulation in the Hippocampus
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Animal Treatment and Unilateral 6-OHDA Lesion in MFB
4.3. Apomorphine-Induced Rotation.
4.4. Immunohistochemistry
4.5. Western Blot and Dot Blot Analysis
4.6. Behavior Test
4.7. Double-Fluorescence Immunostaining of Tissues
4.8. Quantitative Analysis
4.9. Establishment of U6-NOX4 shRNA-CMV-EGFP/AAV and AAV Vector and AAV Viral Package.
4.10. Adeno-Associated Virus 2-Mediated NOX4 Knockdown
4.11. NOX Activity Assay
4.12. Novel Object Recognition Test
4.13. Data Analysis and Statistics
Author Contributions
Acknowledgments
Conflicts of Interest
Abbreviations
NOX4 | NADPH oxidase-4 |
NADPH | Nicotinamide adenine sinucleotide phosphate |
PD | Parkinson’s disease |
PDD | Parkinson’s disease with dementia |
AD | Alzheimer disease |
MCI | Mild cognitive impairment |
MWM | Morris water maze |
NOR | Novel object recognition |
α-syn | Alpha synuclein |
p-α-syn | Phosphorylated alpha-synuclein |
Aβ | Amyloid beta |
Tuj-1 | Neuron-specific class III beta-tubulin |
6-OHDA | 6-hydroxydopamine |
DG | Dentate gyrus |
SN | Substantia nigra |
TH | Tyrosine hydroxylase |
MFB | Medial forebrain bundle |
APO | Apomorphine |
Scb shRNA | Scrambled shRNA/AAV |
rAAV | Recombinant AAV |
EGFP | Enhanced green fluorescent protein |
ANOVA | Analysis of variance |
h | hour(s) |
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Choi, D.-H.; Choi, I.-A.; Lee, C.S.; Yun, J.H.; Lee, J. The Role of NOX4 in Parkinson’s Disease with Dementia. Int. J. Mol. Sci. 2019, 20, 696. https://doi.org/10.3390/ijms20030696
Choi D-H, Choi I-A, Lee CS, Yun JH, Lee J. The Role of NOX4 in Parkinson’s Disease with Dementia. International Journal of Molecular Sciences. 2019; 20(3):696. https://doi.org/10.3390/ijms20030696
Chicago/Turabian StyleChoi, Dong-Hee, In-Ae Choi, Cheol Soon Lee, Ji Hee Yun, and Jongmin Lee. 2019. "The Role of NOX4 in Parkinson’s Disease with Dementia" International Journal of Molecular Sciences 20, no. 3: 696. https://doi.org/10.3390/ijms20030696