Pharmacological modulation of long-term potentiation in animal models of Alzheimer' s disease.

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 Alzheimer s 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.