title: Pharmacological modulation of long-term potentiation in animal models of Alzheimer's disease.
abstract: The discovery of long-term potentiation (LTP) of hippocampal synaptic transmission, which represents a classical model for learning and memory at the cellular level, has stimulated over the past years substantial progress in the understanding of pathogenic mechanisms underlying cognitive disorders, such as Alzheimers disease (AD). Multiple lines of evidence indicate synaptic dysfunction not only as a core feature but also a leading cause of AD. Multiple pathways may play a significant role in the execution of synaptic dysfunction and neuronal death triggered by beta-amyloid (Abeta) in AD. Following intensive investigations into LTP in AD models, a variety of compounds have been found to rescue LTP impairment via numerous molecular mechanisms. Yet very few of these findings have been successfully translated into disease-modifying compounds in humans. This review recapitulates the emerging disease-modifying strategies utilized to modulate hippocampal synaptic plasticity with particular attention to approaches targeting ligand-gated ion channels, G-protein-coupled receptors (GPCRs), Receptor Tyrosine Kinases (RTKs) and epigenetic mechanisms. It is hoped that novel multi-targeted drugs capable of regulating spine plasticity might be effective to counteract the progression of AD and related cognitive syndromes.
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Nistico'
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Piccinin
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Schepisi
authors.affiliation: Pharmacology of Synaptic Plasticity Unit, European Brain Research Institute, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ferraina
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Laurenza
authors.affiliation: Laboratory of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Mango
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Graziani
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Nicoletti
authors.affiliation: Laboratory of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: N B
authors.initials: NB
authors.lastname: Mercuri
authors.affiliation: IRCSS Neuromed, Pozzilli, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Feligioni