Articles: signal-transducing-adaptor-proteins.
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RanBP9 is a multi-domain scaffolding protein known to integrate extracellular signaling with intracellular targets. We previously demonstrated that RanBP9 enhances Aβ generation and amyloid plaque burden which results in loss of specific pre- and postsynaptic proteins in vivo in a transgenic mouse model. Additionally, we showed that the levels of spinophilin, a marker of dendritic spines were inversely proportional to the RanBP9 protein levels within the synaptosomes isolated from AD brains. ⋯ Thus dendritic arbor and spine density were directly correlated to the levels of phosphorylated form of cofilin in the RanBP9 transgenic mice. Similarly, cortical synaptosomes showed a 20% (p<0.01) reduction in the levels of spinophilin in the RanBP9 transgenic mice. These results provided the physical basis for the loss of synaptic proteins by RanBP9 and most importantly it also explains the impaired spatial learning and memory skills previously observed in the RanBP9 transgenic mice.
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Multicenter Study
Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial.
Choroideremia is an X-linked recessive disease that leads to blindness due to mutations in the CHM gene, which encodes the Rab escort protein 1 (REP1). We assessed the effects of retinal gene therapy with an adeno-associated viral (AAV) vector encoding REP1 (AAV.REP1) in patients with this disease. ⋯ UK Department of Health and Wellcome Trust.
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Comparative Study
NEDD9 overexpression correlates with the progression and prognosis in gastric carcinoma.
The aim of this study was to investigate neural precursor cell expressed developmentally down-regulated 9 (NEDD9) expression in human gastric carcinoma (GC) and to explore its clinic significance. NEDD9 expression was detected by immunohistochemistry in GC, their corresponding paracancerous histological normal tissues (PCHNTs), and gastric normal tissues. And this result was further confirmed at the protein and mRNA level by Western blotting and quantitative real-time PCR, respectively. ⋯ And we also detected frequently NEDD9 up-regulation in both protein and mRNA levels in GC tissues as compared to PCHNTs. Kaplan-Meier survival analysis showed that high NEDD9 expression exhibited a significant correlation with poor prognosis for gastric cancer patients. Our data suggested that NEDD9 could be used as prognostic molecular marker to be applied in the clinical setting to diagnosis, evaluating patient's outcome (prognosis and recurrence) for GC patients.
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Prognostic significance of XB130 expression in surgically resected pancreatic ductal adenocarcinoma.
XB130 is a newly discovered adaptor protein for intracellular signal transduction; it is involved in gene regulation, cell proliferation, cell survival, cell migration, and tumorigenesis. However, its expression and role in pancreatic ductal adenocarcinoma (PDAC) have not been investigated. The present study was designed to clarify the prognostic significance of XB130 expression in PDAC. ⋯ XB130 was overexpressed in the PDAC. XB130 is a promising pathological marker for the prediction of outcome in patients with PDAC.