Dysregulation in the Brain Protein Profile of Zebrafish Lacking the Parkinson ’s Disease-Related Protein DJ-1

AbstractDJ-1 is a protein with a wide range of functions importantly related to redox regulation in the cell. In humans, dysfunction of thePARK7 gene is associated with neurodegeneration and Parkinson ’s disease. Our objective was to establish a novel DJ-1 knockout zebrafish line and to identify early brain proteome changes, which could be linked to later pathology. The CRISPR-Cas9 method was used to target exon 1 of thepark7-/- gene to produce a transgenic DJ-1-deficient zebrafish model of Parkinson ’s disease. Label-free mass spectrometry was employed to identify altered protein expression in the DJ-1 null brain of early adult animals. Thepark7−/− line appears to develop normally at young adult and larval stages. With aging however, DJ-1 null fish exhibit lower tyrosine hydroxylase levels, respiratory failure in skeletal muscle, and lower body mass which is especially prevalent among male fish. By proteomic analysis of early adult brains, we determined that less than 5% of the 4091 identified proteins were influenced by the lack of DJ-1. The dysregulated proteins were mainly proteins known to be involved in mitochondrial metabolism, mitophagy, stress response, redox regulation, and inflammation. This dysregulation in protein networks of our novel DJ-1-deficient zebrafish model occurs in the early adult stage preceding a Parkinson ’s disease-related phenotype and the reduction of tyrosine hydroxylase level. The identified protein changes provide...
Source: Molecular Neurobiology - Category: Neurology Source Type: research

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Source: Amino Acids - Category: Biochemistry Authors: Tags: Amino Acids Source Type: research
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Source: Journal of Molecular Biology - Category: Molecular Biology Source Type: research
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Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Review Source Type: research
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Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
In this study, astrocytic Kir6.1 knockout (KO) mice were used to examine the effect of astrocytic Kir6.1/K-ATP channel on dopaminergic (DA) neurodegeneration triggered by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Here, we found that astrocytic Kir6.1 KO mice showed more DA neuron loss in substantia nigra compacta (SNc), lower level of dopamine in the striatum, and more severe motor dysfunction than controls. Interestingly, this companied by increased neuroinflammation and decreased autophagy level in SNc in vivo and astrocytes in vitro. Mechanistically, astrocytic Kir6.1 KO inhibited mitophagy which resu...
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Source: Mitochondrion - Category: Biochemistry Source Type: research
In this study, astrocytic Kir6.1 knockout (KO) mice were used to examine the effect of astrocytic Kir6.1/K-ATP channel on dopaminergic (DA) neurodegeneration triggered by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Here, we found that astrocytic Kir6.1 KO mice showed more DA neuron loss in substantia nigra compacta (SNc), lower level of dopamine in the striatum, and more severe motor dysfunction than controls. Interestingly, this companied by increased neuroinflammation and decreased autophagy level in SNc in vivo and astrocytes in vitro. Mechanistically, astrocytic Kir6.1 KO inhibited mitophagy which resu...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research
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Source: Environmental Research - Category: Environmental Health Authors: Tags: Environ Res Source Type: research
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Source: Biological Chemistry - Category: Chemistry Tags: Biol Chem Source Type: research
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