PUBLICATION

Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration

Authors
Wasel, O., Freeman, J.L.
ID
ZDB-PUB-200823-5
Date
2020
Source
International Journal of Molecular Sciences   21(17): (Review)
Registered Authors
Freeman, Jennifer
Keywords
MPTP, Parkinson’s disease, dj1, dopamine, neurotransmission, paraquat, pink1, prkn, rotenone, zebrafish
MeSH Terms
  • Animals
  • Disease Models, Animal
  • Dopamine/metabolism
  • Dopaminergic Neurons/drug effects
  • Dopaminergic Neurons/pathology*
  • Gene Knockdown Techniques
  • Neurotoxicity Syndromes/etiology*
  • Neurotoxicity Syndromes/pathology
  • Neurotoxicity Syndromes/therapy
  • Oxidopamine/toxicity
  • Paraquat/toxicity
  • Parkinson Disease/genetics*
  • Parkinson Disease/pathology
  • Parkinson Disease/therapy
  • Parkinsonian Disorders/etiology
  • Parkinsonian Disorders/therapy
  • Protein Serine-Threonine Kinases/genetics
  • Rotenone/toxicity
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
32825242 Full text @ Int. J. Mol. Sci.
Abstract
The zebrafish (Danio rerio) is routinely used in biological studies as a vertebrate model system that provides unique strengths allowing applications in studies of neurodevelopmental and neurodegenerative diseases. One specific advantage is that the neurotransmitter systems are highly conserved throughout vertebrate evolution, including between zebrafish and humans. Disruption of the dopaminergic signaling pathway is linked to multiple neurological disorders. One of the most common is Parkinson's disease, a neurodegenerative disease associated with the loss of dopaminergic neurons, among other neuropathological characteristics. In this review, the development of the zebrafish's dopaminergic system, focusing on genetic control of the dopaminergic system, is detailed. Second, neurotoxicant models used to study dopaminergic neuronal loss, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the pesticides paraquat and rotenone, and 6-hydroxydopamine (6-OHDA), are described. Next, zebrafish genetic knockdown models of dj1, pink1, and prkn established for investigating mechanisms of Parkinson's disease are discussed. Chemical modulators of the dopaminergic system are also highlighted to showcase the applicability of the zebrafish to identify mechanisms and treatments for neurodegenerative diseases such as Parkinson's disease associated with the dopaminergic system.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes