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Trisomy for Synaptojanin1 in Down syndrome is functionally linked to the enlargement of early endosomes
Thu Apr 19 19:35:42 BST 2012
Key Topics

Click on any of the topic names to view its own newsletter. The text we matched to the topic is shown in grey underneath.

 SYNJ1, synaptojanin 1  

[matched:synaptojanin1, synj1, synaptojanin 1]

 Down Syndrome  

[matched:down syndrome]

Other Topics Mentioned

Less relevant than those above but listed here for convenience.


 Neuroblastoma  

[matched:neuroblastoma]

 Alzheimer Disease  

[matched:alzheimer s disease]

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Enlarged early endosomes have been observed in neurons and fibroblasts in Down syndrome (DS). These endosome abnormalities have been implicated in the early development of Alzheimer's disease (AD) pathology in these subjects. Here, we show the presence of enlarged endosomes in blood mononuclear cells and lymphoblastoid cells lines (LCLs) from individuals with DS using immunofluorescence and confocal microscopy. Genotype-phenotype correlations in LCLs carrying partial trisomies 21 revealed that triplication of a 2.56 Mb locus in 21q22.11 is associated with the endosomal abnormalities. This locus contains the gene encoding the phosphoinositide phosphatase synaptojanin 1 (SYNJ1), a key regulator of the signalling phospholipid phosphatidylinositol-4,5-biphosphate that has been shown to regulate clathrin-mediated endocytosis. We found that SYNJ1 transcripts are increased in LCLs from individuals with DS and that overexpression of SYNJ1 in a neuroblastoma cell line as well as in transgenic mice leads to enlarged endosomes. Moreover the proportion of enlarged endosomes in fibroblasts from an individual with DS was reduced after silencing SYNJ1 expression with RNA interference. In LCLs carrying APP microduplications causing autosomal dominant early-onset AD, enlarged endosomes were absent, suggesting that APP overexpression alone is not involved in the modification of early endosomes in this cell type. These findings provide new insights into the contribution of SYNJ1 overexpression to the endosomal changes observed in DS and suggest an attractive new target for rescuing endocytic dysfunction and lipid metabolism in DS and in AD;   Read more on this story here

Source: ncbi.nlm.nih.gov   (view original)
Inst: Centre de Recherche de l'Institut du Cerveau et de la Moelle, CNRS UMR7225, UPMC, INSERM UMRS975, Hopital Pitie-Salpetriere, Paris, France.
   abstracted provided by MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

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