| RRC ID |
47654
|
| 著者 |
Hindle SJ, Hebbar S, Schwudke D, Elliott CJH, Sweeney ST.
|
| タイトル |
A saposin deficiency model in Drosophila: Lysosomal storage, progressive neurodegeneration and sensory physiological decline.
|
| ジャーナル |
Neurobiol Dis
|
| Abstract |
Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases that mediate the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence or impaired function of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids. The pathological events leading to neuronal dysfunction induced by lysosomal storage of sphingolipids are as yet poorly defined. We have generated and characterised a Drosophila model of saposin deficiency that shows striking similarities to the human diseases. Drosophila saposin-related (dSap-r) mutants show a reduced longevity, progressive neurodegeneration, lysosomal storage, dramatic swelling of neuronal soma, perturbations in sphingolipid catabolism, and sensory physiological deterioration. Our data suggests a genetic interaction with a calcium exchanger (Calx) pointing to a possible calcium homeostasis deficit in dSap-r mutants. Together these findings support the use of dSap-r mutants in advancing our understanding of the cellular pathology implicated in saposin deficiency and related LSDs.
|
| 巻・号 |
98
|
| ページ |
77-87
|
| 公開日 |
2017-2-1
|
| DOI |
10.1016/j.nbd.2016.11.012
|
| PII |
S0969-9961(16)30280-7
|
| PMID |
27913291
|
| PMC |
PMC5319729
|
| MeSH |
Aging / metabolism
Aging / pathology
Animals
Animals, Genetically Modified
Antiporters / genetics
Antiporters / metabolism
Brain / metabolism
Brain / pathology
Calcium / metabolism
Ceramides / metabolism
Disease Models, Animal*
Drosophila Proteins / deficiency*
Drosophila Proteins / genetics
Drosophila Proteins / metabolism
Drosophila melanogaster
Homeostasis / physiology
Lysosomal Storage Diseases, Nervous System / metabolism*
Lysosomal Storage Diseases, Nervous System / pathology
Neurodegenerative Diseases / metabolism*
Neurodegenerative Diseases / pathology
Neuroglia / metabolism
Neuroglia / pathology
Neurons / metabolism
Neurons / pathology
Phenotype
Saposins / deficiency*
Saposins / genetics
Sphingosine / metabolism
Survival Analysis
|
| IF |
5.332
|
| 引用数 |
4
|
|
WOS 分野
|
NEUROSCIENCES
|
| リソース情報 |
| ショウジョウバエ |
DGRC#105467 |
