1. From the multifactorial nature of Alzheimer`s disease to multitarget therapy: the contribution of the translational approach.
- Author
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Calzà L, Baldassarro VA, Giuliani A, Lorenzini L, Fernandez M, Mangano C, Sivilia S, Alessandri M, Gusciglio M, Torricella R, and Giardino L
- Subjects
- Alzheimer Disease metabolism, Alzheimer Disease physiopathology, Amyloid Precursor Protein Secretases antagonists & inhibitors, Amyloid Precursor Protein Secretases metabolism, Animals, Anti-Inflammatory Agents therapeutic use, Cyclopropanes therapeutic use, Drug Design, Enzyme Inhibitors therapeutic use, Flurbiprofen chemical synthesis, Flurbiprofen therapeutic use, Humans, Inflammation drug therapy, Mice, Mice, Transgenic, Nootropic Agents therapeutic use, Synapses drug effects, Synapses pathology, Synaptic Transmission drug effects, Translational Research, Biomedical, Alzheimer Disease drug therapy, Anti-Inflammatory Agents chemical synthesis, Cyclopropanes chemical synthesis, Enzyme Inhibitors chemical synthesis, Flurbiprofen analogs & derivatives, Nootropic Agents chemical synthesis
- 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.
- Published
- 2013
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