Anti-Tau (V256) Antibody (A25381)

Lack of effective biomarkers is one of the challenges in current chemotherapy to predict drug response and sensitivity. This study was carried out to investigate the relationships between the expressions of class III β-tubulin, microtubule-associated protein tau (MAPT), survivin, and the sensitivity of primary gastric cancer (GC) to paclitaxel treatment. Reverse transcription PCR and Western blot were used to evaluate the mRNA and protein expressions of class III β-tubulin, MAPT, and survivin in fifty-four GC tissues. Viable tumor cells from gastric carcinomas were tested for their sensitivity to paclitaxel using adenosine triphosphate-based tumor chemosensitivity assay in vitro. Out of 54 samples, 30 samples were sensitive to paclitaxel, while the other 24 samples were resistant. The overall efficacy of paclitaxel was 55.56% (30/54). The mRNA expressions of class III β-tubulin and survivin were significantly correlated with the histological grade (P = 0.029, 0.009, respectively). The sensitivity of GC patients to paclitaxel treatment was inversely correlated with the mRNA and protein expressions of class III β-tubulin (P < 0.01), MAPT (P < 0.05), and survivin (P < 0.05). A significant positive correlation was found between class III β-tubulin and MAPT expression at mRNA and protein levels (mRNA: P = 0.037; protein: P = 0.001). Our results indicate that the expression levels of class III β-tubulin, MAPT, and survivin are good biomarkers for predicting the sensitivity of GC to paclitaxel treatment.

Recent evidence indicates that severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to take a pivotal role in early sporadic Alzheimer's disease pathology. It has been reported that naringenin (NAR), derived from citrus aurantium, exhibits antioxidant potential and protects the brain against neurodegeneration. The current study was designed to further investigate the protective effect of the NAR on neurodegeneration in a rat model of AD induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ), and to determine whether this neuroprotective effect was associated with brain insulin signaling. Rats were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle and then supplemented with NAR (25, 50 mg, 100 mg/kg, respectively) for 3 weeks. The ICV-STZ injected rats did not have elevated blood glucose levels. 21 days following ICV-STZ injection, rats treated with NAR had better learning and memory performance in the Morris water maze test compared with rats treated with saline. We demonstrated that NAR increased the mRNA expression of INS and INSR in cerebral cortex and hippocampus. In addition, NAR reversed ICV-STZ induced Tau hyper-phosphorylation in both hippocampus and cerebral cortex through downregulation of glycogen synthase kinase-3β (GSK-3β) activity, a key kinase in the insulin signaling. Brain levels of Abeta, which were elevated in ICV-STZ rats, were significantly reduced in NAR-treated rats via upregulation of insulin degrading enzyme. These effects were mediated by increased insulin and insulin receptors expression in the brain, suggesting that insulin sensitizer agents might have therapeutic efficacy in early AD.

Ubiquitin C-terminal hydrolase L1 (UCH-L1) is abundantly expressed in the brain and is critical for the normal function of synapses. cAMP response element binding protein (CREB) is a transcription factor which initiates the expression of proteins that related to the regulation of synaptic plasticity and memory function. Studies have shown that UCH-L1 can influence the expression and activity of CREB, but the underlying mechanisms remain unclear. In this study, we used UCH-L1 inhibitor LDN to treat mice hippocampal slices and found that UCH-L1 inhibition caused the dephosphorylation of CREB at Ser133 site. Meanwhile, hyperphosphorylation of microtubule-associated protein tau; increased expression of synaptic protein components of PSD-95 and synapsin-1, and decreased activity of tyrosine kinase Fyn were observed after UCH-L1 inhibition. Moreover, all these alternations have an influence on the normal function of N-methyl-D-aspartate (NMDA) receptor NR2B subunit which is likely to result in the dephosphorylation of CREB. We also found that LDN treatment mediated protein kinase A (PKA) deactivation was involved in the dephosphorylation of CREB. Thus, our study introduces a novel possible mechanism for elaborating the effects of UCH-L1 inhibition on the CREB activity and the implicated signaling pathways.