Document Detail


Motor deficit in a Drosophila model of mucolipidosis type IV due to defective clearance of apoptotic cells.
MedLine Citation:
PMID:  19041749     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Disruption of the Transient Receptor Potential (TRP) mucolipin 1 (TRPML1) channel results in the neurodegenerative disorder mucolipidosis type IV (MLIV), a lysosomal storage disease with severe motor impairments. The mechanisms underlying MLIV are poorly understood and there is no treatment. Here, we report a Drosophila MLIV model, which recapitulates the key disease features, including abnormal intracellular accumulation of macromolecules, motor defects, and neurodegeneration. The basis for the buildup of macromolecules was defective autophagy, which resulted in oxidative stress and impaired synaptic transmission. Late-apoptotic cells accumulated in trpml mutant brains, suggesting diminished cell clearance. The accumulation of late-apoptotic cells and motor deficits were suppressed by expression of trpml(+) in neurons, glia, or hematopoietic cells. We conclude that the neurodegeneration and motor defects result primarily from decreased clearance of apoptotic cells. Since hematopoietic cells in humans are involved in clearance of apoptotic cells, our results raise the possibility that bone marrow transplantation may limit the progression of MLIV.
Authors:
Kartik Venkatachalam; A Ashleigh Long; Rebecca Elsaesser; Daria Nikolaeva; Kendal Broadie; Craig Montell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  135     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-12-01     Completed Date:  2008-12-19     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  838-51     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Disease Models, Animal*
Drosophila / metabolism*
Humans
Mucolipidoses / metabolism*
Neurodegenerative Diseases / metabolism
TRPM Cation Channels / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
EY08117/EY/NEI NIH HHS; NS41740/NS/NINDS NIH HHS; R01 EY008117/EY/NEI NIH HHS; R01 EY008117-20/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/TRPM Cation Channels
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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