Linked Life Data

19439422

Source:http://linkedlifedata.com/resource/pubmed/id/19439422

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 6
pubmed:dateCreated
2009-5-26
pubmed:abstractText
Currently, only symptomatic therapy is available for Parkinson's disease. The zebrafish is a vertebrate animal model ideally suited for high throughput compound screening to identify disease-modifying compounds for Parkinson's disease. We have developed a zebrafish model for Parkin deficiency, the most commonly mutated gene in early onset Parkinson's disease. The zebrafish Parkin protein is 62% identical to its human counterpart with 78% identity in functionally relevant regions. The parkin gene is expressed throughout zebrafish development and ubiquitously in adult zebrafish tissue. Abrogation of Parkin activity leads to a significant decrease in the number of ascending dopaminergic neurons in the posterior tuberculum (homologous to the substantia nigra in humans), an effect enhanced by exposure to MPP+. Both light microscopic analysis and staining with the pan-neuronal marker HuC confirmed that this loss of dopaminergic neurons is not due to general impairment of brain development. Neither serotonergic nor motor neurons were affected, further emphasizing that the effect of parkin knockdown appears to be specific for dopaminergic neurons. Notably, parkin knockdown zebrafish embryos also develop specific reduction in the activity of the mitochondrial respiratory chain complex I, making this the first vertebrate model to share both important pathogenic mechanisms (i.e. complex I deficiency) and the pathological hallmark (i.e. dopaminergic cell loss) with human parkin-mutant patients. The zebrafish model is thus ideally suited for future drug screens and other studies investigating the functional mechanisms underlying neuronal cell death in early onset Parkinson's Disease. Additional electron microscopy studies revealed electron dense material in the t-tubules within the muscle tissue of parkin knockdown zebrafish. T-tubules are rich in L-type calcium channels, therefore our work might also provide a tentative link between genetically determined early onset Parkinson's disease and recent studies attributing an important role to these L-type calcium channels in late onset sporadic Parkinson's disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1460-2156
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
132
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1613-23
pubmed:meshHeading
pubmed-meshheading:19439422-Animals, pubmed-meshheading:19439422-Conserved Sequence, pubmed-meshheading:19439422-Disease Models, Animal, pubmed-meshheading:19439422-Dopamine, pubmed-meshheading:19439422-Drug Evaluation, Preclinical, pubmed-meshheading:19439422-Electron Transport Complex I, pubmed-meshheading:19439422-Embryonic Development, pubmed-meshheading:19439422-Exons, pubmed-meshheading:19439422-Gene Knockdown Techniques, pubmed-meshheading:19439422-Microscopy, Electron, pubmed-meshheading:19439422-Mitochondria, Muscle, pubmed-meshheading:19439422-Mitochondrial Diseases, pubmed-meshheading:19439422-Neurons, pubmed-meshheading:19439422-Oligonucleotides, Antisense, pubmed-meshheading:19439422-Parkinson Disease, pubmed-meshheading:19439422-RNA Splice Sites, pubmed-meshheading:19439422-Substantia Nigra, pubmed-meshheading:19439422-Swimming, pubmed-meshheading:19439422-Ubiquitin-Protein Ligases, pubmed-meshheading:19439422-Zebrafish
pubmed:year
2009
pubmed:articleTitle
Complex I deficiency and dopaminergic neuronal cell loss in parkin-deficient zebrafish (Danio rerio).
pubmed:affiliation
Academic Neurology Unit, Medical School, University of Sheffield, Beech Hill Road, Sheffield, UK. o.bandmann@sheffield.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't