Abstract
The drug discovery for disease-modifying agents in Alzheimer disease (AD) is facing a failure of clinical trials with drugs based on two driving hypotheses, i.e. the cholinergic and amyloidogenic hypotheses. In this article we recapitulate the main aspects of AD pathology, focusing on possible mechanisms for synaptic dysfunction, neurodegeneration and inflammation. We then present the pharmacological and neurobiological profile of a novel compound (CHF5074) showing both anti-inflammatory and gamma-secretase modulatory activities, discussing the possible time-window for effective treatment in an AD transgenic mouse model. Finally, the concept of cognitive reserve is introduced as possible target for preventive therapies.
Keywords: Tg2576, amyloid precursor protein, cognitive reserve, neuroinflammation, translational medicine.
Current Topics in Medicinal Chemistry
Title:From the Multifactorial Nature of Alzheimer`s Disease to Multitarget Therapy: The Contribution of the Translational Approach
Volume: 13 Issue: 15
Author(s): Laura Calzà, Vito Antonio Baldassarro, Alessandro Giuliani, Luca Lorenzini, Mercedes Fernandez, Chiara Mangano, Sandra Sivilia, Marco Alessandri, Marco Gusciglio, Roberta Torricella and Luciana Giardino
Affiliation:
Keywords: Tg2576, amyloid precursor protein, cognitive reserve, neuroinflammation, translational medicine.
Abstract: The drug discovery for disease-modifying agents in Alzheimer disease (AD) is facing a failure of clinical trials with drugs based on two driving hypotheses, i.e. the cholinergic and amyloidogenic hypotheses. In this article we recapitulate the main aspects of AD pathology, focusing on possible mechanisms for synaptic dysfunction, neurodegeneration and inflammation. We then present the pharmacological and neurobiological profile of a novel compound (CHF5074) showing both anti-inflammatory and gamma-secretase modulatory activities, discussing the possible time-window for effective treatment in an AD transgenic mouse model. Finally, the concept of cognitive reserve is introduced as possible target for preventive therapies.
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Calzà Laura, Baldassarro Antonio Vito, Giuliani Alessandro, Lorenzini Luca, Fernandez Mercedes, Mangano Chiara, Sivilia Sandra, Alessandri Marco, Gusciglio Marco, Torricella Roberta and Giardino Luciana, From the Multifactorial Nature of Alzheimer`s Disease to Multitarget Therapy: The Contribution of the Translational Approach, Current Topics in Medicinal Chemistry 2013; 13 (15) . https://dx.doi.org/10.2174/15680266113139990140
DOI https://dx.doi.org/10.2174/15680266113139990140 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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