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

Robert Nisticò, S. Piccinin, C. Schepisi, C. Ferraina, M. Laurenza, D. Mango, M. Graziani, F. Nicoletti, N. B. Mercuri, M. Feligioni

Research output: Contribution to journalArticle

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 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 (Aβ) 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.

Original languageEnglish
Pages (from-to)37-47
Number of pages11
JournalJournal of Biological Regulators and Homeostatic Agents
Volume27
Issue number2 SUPPL.
Publication statusPublished - Apr 2013

Keywords

  • Alzheimer's disease
  • Hippocampus
  • Long-term potentiation
  • Synaptic plasticity

ASJC Scopus subject areas

  • Oncology
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Immunology and Allergy
  • Immunology
  • Endocrinology
  • Physiology
  • Cancer Research

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    Nisticò, R., Piccinin, S., Schepisi, C., Ferraina, C., Laurenza, M., Mango, D., Graziani, M., Nicoletti, F., Mercuri, N. B., & Feligioni, M. (2013). Pharmacological modulation of long-term potentiation in animal models of Alzheimer's disease. Journal of Biological Regulators and Homeostatic Agents, 27(2 SUPPL.), 37-47.