Bateman R.J.,University of Washington |
Aisen P.S.,University of California at San Diego |
De Strooper B.,Vlaams Institute for Biotechnology |
De Strooper B.,Catholic University of Leuven |
And 7 more authors.
Alzheimer's Research and Therapy | Year: 2011
Autosomal-dominant Alzheimer's disease has provided significant understanding of the pathophysiology of Alzheimer's disease. The present review summarizes clinical, pathological, imaging, biochemical, and molecular studies of autosomal-dominant Alzheimer's disease, highlighting the similarities and differences between the dominantly inherited form of Alzheimer's disease and the more common sporadic form of Alzheimer's disease. Current developments in autosomal-dominant Alzheimer's disease are presented, including the international Dominantly Inherited Alzheimer Network and this network's initiative for clinical trials. Clinical trials in autosomal-dominant Alzheimer's disease may test the amyloid hypothesis, determine the timing of treatment, and lead the way to Alzheimer's disease prevention. © 2011 BioMed Central Ltd.
Bolognesi M.L.,University of Bologna |
Chiriano G.,International School for Advanced Studies |
Bartolini M.,University of Bologna |
Mancini F.,University of Bologna |
And 10 more authors.
Journal of Medicinal Chemistry | Year: 2011
Eight monomeric congeners, related to the multitarget lead candidate memoquin, were prepared and evaluated at multiple targets to determine their profile against Alzheimer's disease. 2-4 bind to AChE with similar low nanomolar affinities and function as effective inhibitors of amyloid aggregation. The most potent monovalent ligand 2 also inhibits BACE-1 in vitro and APP metabolism in primary chicken telencephalic neurons. (Figure presented) © 2011 American Chemical Society.
Rosini M.,University of Bologna |
Simoni E.,University of Bologna |
Bartolini M.,University of Bologna |
Soriano E.,Institute Quimica Organica General CSIC |
And 8 more authors.
ChemMedChem | Year: 2013
Inspired by the concept of bivalent ligands, we prepared a small set of analogues of the drug candidate dimebon. They were shown to inhibit AChE, Aβ42 aggregation, and NMDA receptor activation to a greater extent than dimebon. Some of these compounds also enhanced the survival of chicken neurons under apoptosis-inducing conditions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PubMed | JSW Lifesciences GmbH
Type: Comparative Study | Journal: Journal of molecular neuroscience : MN | Year: 2011
Sequential cleavage of amyloid precursor protein (APP) by - and -secretases and the formation of A peptides are pivotal for Alzheimers disease. Therefore, a large number of drugs has been developed targeting APP metabolism. However, many pharmacological compounds have been identified in vitro in immortalized APP overexpressing cell lines rather than in primary neurons. Here, we compared the effect of already characterized secretase inhibitors and modulators on A formation in primary chicken telencephalic neurons and in a human neuroglioma cell line (H4) ectopically expressing human APP with the Swedish double mutation. Primary chicken neurons replicated the effects of a -secretase inhibitor (-secretase inhibitor IV), two -secretase inhibitors (DAPM, DAPT), two non-steroidal-anti-inflammatory drugs (sulindac sulfide, CW), and of the calpain inhibitor calpeptin. With the exception of the two -secretase inhibitors, all tested compounds were more efficacious in primary chicken telencephalic neurons than in the immortalized H4 cell line. Moreover, H4 cells failed to reproduce the effect of calpeptin. Hence, primary chicken telencephalic neurons represent a suitable cell culture model for testing drugs interfering with APP processing and are overall more sensitive to pharmacological interference than immortalized H4 cells ectopically expressing mutant human APP.