A New Tacrine-Melatonin Hybrid Reduces Amyloid Burden and Behavioral Deficits in a Mouse Model of Alzheimer's Disease

作者：Spuch Carlos; Antequera Desiree; Isabel Fernandez Bachiller M; Isabel Rodriguez Franco M; Carro Eva^*

来源：Neurotoxicity Research, 2010, 17(4): 421-431.

DOI：10.1007/s12640-009-9121-2

• Transgenic mice
• Cytotoxicity
• Alzheimer's disease
• Amyloid
• Hybrid

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 (A beta)-induced cell death and amyloid burden in the brain parenchyma of APP/Ps1 mice. This reduction in A beta pathology was accompanied by a recovery in cognitive function. Since this tacrine-melatonin hybrid apparently reduces brain A beta and behavioral deficits, we believe this drug has remarkable and significant neuroprotective effects and might be considered a potential therapeutic strategy in AD.

• 出版日期2010-5