Mesoporous Si@carbon core-shell nanowires with a diameter of approximately 6.5 nm were prepared for a lithium battery anode material using a SBA-15 template. As-synthesized nanowires demonstrated excellent first charge capacity of 3163 mA h/g with a Coulombic efficiency of 86% at a rate of 0.2 C (600 mA/g) between 1.5 and 0 V in coin-type half-cells. Moreover, the capacity retention after 80 cycles was 87% and the rate capability at 2 C (6000 mA/g) was 78% the capacity at 0.2 C.
The AICD (amyloid precursor protein [APP] intracellular domain) and C31, the caspase-cleaved C-terminal fragment of APP, have been found in the brains of patients with Alzheimer's disease (AD). Here, we demonstrate for the first time that the C-terminal fragments of APP (AICD [C57, C59] and C31) exert neurotoxicity on differentiated PC 12 cells and rat primary cortical neurons by inducing the expression of glycogen synthase kinase 3beta, forming a ternary complex with Fe65 and CP2/LSF/LBP1 in the nucleus, whereas deletion mutants and a point mutant with Y682G of the YENPTY domain, a Fe65 binding domain, do not. Moreover, expression of APP770 and Swedish mutant form of APP increased the levels of C-terminal fragments of APP (APP-CTs) in neuronal cells and also induced the up-regulation of glycogen synthase kinase-3beta at both the mRNA and the protein levels. In addition, we show that CP2/LSF/LBP1 binding site (nt +0 to approximately +10) in human glycogen synthase kinase 3beta promoter region is essential for the induction of the gene transcription by APP-CTs. The neurotoxicities induced by APP-CTs (AICD and C31) were accompanied by an increase in the active form of glycogen synthase kinase-3beta, and by the induction of tau phosphorylation and a reduction in nuclear beta-catenin levels, and led to apoptosis.
Minocycline is a semi-synthetic tetracycline antibiotic that effectively crosses the blood-brain barrier. Minocycline has been reported to have significant neuroprotective effects in models of cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, and Huntington's and Parkinson's diseases. In this study, we demonstrate that minocycline has neuroprotective effects in in vitro and in vivo Alzheimer's disease models. Minocycline was found to attenuate the increases in the phosphorylation of double-stranded RNAdependent serine/threonine protein kinase, eukaryotic translation initiation factor-2 a and caspase 12 activation induced by amyloid b peptide 1-42 treatment in NGF-differentiated PC 12 cells. In addition, increases in the phosphorylation of eukaryotic translation initiation factor-2 a were attenuated by administration of minocycline in Tg2576 mice, which harbor mutated human APP695 gene including the Swedish double mutation and amyloid b peptide 1-42 -infused rats. We found that minocycline administration attenuated deficits in learning and memory in amyloid b peptide 1-42 -infused rats. Increased phosphorylated state of eukaryotic translation initiation factor-2 a is observed in Alzheimer's disease patients' brains and may result in impairment of cognitive functions in Alzheimer's disease patients by decreasing the efficacy of de novo protein synthesis required for synaptic plasticity. On the basis of these results, minocycline may prove to be a good candidate as an effective therapeutic agent for Alzheimer's disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.