Document Detail


Loss of LRRK2/PARK8 induces degeneration of dopaminergic neurons in Drosophila.
MedLine Citation:
PMID:  17498648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mutations in LRRK2/PARK8 are linked to autosomal dominant forms of Parkinson's disease, but the pathogenic mechanism of LRRK2-associated Parkinson's disease is not fully understood. Moreover, in vivo functions of LRRK2 have not been addressed so far. Thus, we generated and characterized transgenic animals and loss-of-function mutants for LRRK, a sole Drosophila orthologue of human LRRK2. While transgenic expression of pathogenic mutant and wild type LRRK did not show any significant defects, LRRK loss-of-function mutants exhibited severely impaired locomotive activity. Moreover, dopaminergic neurons in LRRK mutants showed a severe reduction in tyrosine hydroxylase immunostaining and shrunken morphology, implicating their degeneration in the mutants. Collectively, our findings unprecedentedly show in vivo that LRRK2 is critical for the integrity of dopaminergic neurons and intact locomotive activity in Drosophila.
Authors:
Sung Bae Lee; Wonho Kim; Sungkyu Lee; Jongkyeong Chung
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Publication Detail:
Type:  Journal Article     Date:  2007-05-04
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  358     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-22     Completed Date:  2007-07-11     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  534-9     Citation Subset:  IM    
Affiliation:
National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Kusong-Dong, Yusong-Gu, Taejon, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Cells, Cultured
Dopamine / metabolism
Drosophila / genetics,  metabolism*
Drosophila Proteins / genetics,  metabolism*
Neurodegenerative Diseases / metabolism*,  pathology*
Neurons / metabolism*,  pathology*
Protein-Serine-Threonine Kinases / genetics,  metabolism*
Receptors, Dopamine / metabolism*
Chemical
Reg. No./Substance:
0/Drosophila Proteins; 0/Receptors, Dopamine; EC 2.7.11.1/LRRK protein, Drosophila; EC 2.7.11.1/LRRK2 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases

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