The data suggest that the DCN may

be used as a target to suppress tinnitus through a bottom-up neuromodulation approach. The underlying mechanism of DCN-stimulation-induced tinnitus suppression was discussed by comparing it with other stimulation modalities. (C) 2012 Elsevier Ireland Ltd. All rights reserved.”
“Genetic and biochemical studies suggest that Alzheimer’s disease (AD) is caused by a series of events initiated by the production and subsequent aggregation of the Alzheimer’s amyloid beta peptide (A beta), the so-called amyloid cascade hypothesis. Thus, a logical approach to treating AD is the development of small molecule inhibitors that either block the proteases that generate A beta from Blebbistatin ic50 its precursor check details (beta- and gamma-secretases) or interrupt and/or reverse A beta aggregation. To identify potent inhibitors of A beta aggregation, we have developed a high-throughput screen based on an earlier selection that effectively paired the folding quality control feature of the Escherichia coli Tat

protein export system with aggregation of the 42-residue AD pathogenesis effecter A beta 42. Specifically, a tripartite fusion between the Tat-dependent export signal ssTorA, the A beta 42 peptide and the beta-lactamase (Bla) reporter enzyme was found to be export incompetent due to aggregation of the A beta 42 moiety. Here, we reasoned that small, cell-permeable molecules that inhibited A beta 42 aggregation would render the ssTorA-A beta 42-Bla chimera competent for Tat export to the periplasm Cyclic nucleotide phosphodiesterase where Bla

is active against b- lactam antibiotics such as ampicillin. Using a fluorescence-based version of our assay, we screened a library of triazine derivatives and isolated four nontoxic, cell-permeable compounds that promoted efficient Tat-dependent export of ssTorA-A beta 42-Bla. Each of these was subsequently shown to be a bona fide inhibitor of A beta 42 aggregation using a standard thioflavin T fibrillization assay, thereby highlighting the utility of our bacterial assay as a useful screen for antiaggregation factors under physiological conditions.”
“The survival activity of adenosine Am agonist CGS21680 on motoneurons in culture through the transactivation of neurotrophin receptor TrkB has been reported previously: however, since adenosine A(2A) receptor belongs to a Gs-protein-coupled receptor, we investigated the involvement of the cAMP pathway in the survival activity of CGS21680 using purified motoneurons in culture. CGS21680 alone showed only small survival activity, but the activity was significantly enhanced by the addition of a phosphodiesterase inhibitor, IBMX. This survival activity was partially inhibited by a protein kinase A inhibitor H89 or a neurotrophin receptor tyrosine kinase inhibitor K252a, and was completely inhibited by their combination.