A new tacrine-melatonin hybrid reduces amyloid burden and behavioral deficits in a mouse model of Alzheimer's disease.
Alzheimer's disease (AD) is a progressive degenerative disorder characterized by the presence of amyloid deposits, neurofibrillary tangles and neuron loss. Emerging evidence indicates that antioxidants could be useful either for the prevention or treatment of AD. Tacrine and melatonin are well-known drugs which act as an acetylcholinesterase inhibitor and a free radical scavenger, respectively. In this study, we evaluated the effects of a new tacrine-melatonin hybrid on behavior and the biochemical and neuropathologic changes observed in amyloid precursor protein/presenilin 1 (APP/Ps1) transgenic mice. Our findings showed that direct intracerebral administration of this hybrid decreased amyloid beta peptide (Abeta)-induced cell death and amyloid burden in the brain parenchyma of APP/Ps1 mice. This reduction in Abeta pathology was accompanied by a recovery in cognitive function. Since this tacrine-melatonin hybrid apparently reduces brain Abeta and behavioral deficits, we believe this drug has remarkable and significant neuroprotective effects and might be considered a potential therapeutic strategy in AD.
Neuroscience Laboratory, University Hospital, 12 de Octubre Research Center, 28041 Madrid, Spain.
Carlos
C
Spuch
Desiree
D
Antequera
M
M
Isabel Fernandez-Bachiller
M
M
Isabel Rodríguez-Franco
Eva
E
Carro
D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D000682:Amyloid / Q000378:metabolism* / Q000633:toxicity; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001526:Behavioral Symptoms / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D001921:Brain / Q000166:cytology; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004338:Drug Combinations; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009924:Organ Culture Techniques; D053764:Presenilin-1 / Q000235:genetics; D051381:Rats; D013619:Tacrine / Q000627:therapeutic use*; D013997:Time Factors
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D004338:Drug Combinations; D018696:Neuroprotective Agents; C508853:PSEN1 protein, human; D053764:Presenilin-1; D013619:Tacrine; D020169:Caspases; D008550:Melatonin