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.
Calzà L, Baldassarro VA, Giuliani A, Lorenzini L, Fernandez M, Mangano C, et al. (2013). From the multifactorial nature of Alzheimer`s disease to multitarget therapy: the contribution of the translational approach. CURRENT TOPICS IN MEDICINAL CHEMISTRY, 13(15), 1843-1852.
From the multifactorial nature of Alzheimer`s disease to multitarget therapy: the contribution of the translational approach
CALZA', LAURA;BALDASSARRO, VITO ANTONIO;GIULIANI, ALESSANDRO;LORENZINI, LUCA;FERNANDEZ CANALES, MARIA DE LAS MERCEDES;MANGANO, CHIARA;SIVILIA, SANDRA;TORRICELLA, ROBERTA;GIARDINO, LUCIANA
2013
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
