From the Multifactorial Nature of Alzheimer`s Disease to Multitarget Therapy: The Contribution of the Translational Approach

Author(s): Laura Calzà, Vito Antonio Baldassarro, Alessandro Giuliani, Luca Lorenzini, Mercedes Fernandez, Chiara Mangano, Sandra Sivilia, Marco Alessandri, Marco Gusciglio, Roberta Torricella, Luciana Giardino.

Journal Name: Current Topics in Medicinal Chemistry

Volume 13 , Issue 15 , 2013

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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.

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Article Details

VOLUME: 13
ISSUE: 15
Year: 2013
Page: [1843 - 1852]
Pages: 10
DOI: 10.2174/15680266113139990140
Price: $58

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