The effect of neuropeptide Y on cell survival and neurotrophin expression in in-vitro models of Alzheimer?s disease

Francesco Angelucci, Francesca Gelfo, Marco Fiore, Nicoletta Croce, Aleksander A. Mathé, Sergio Bernardini, Carlo Caltagirone

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) is a disorder characterized by the accumulation of abnormally folded protein fragments in neurons, i.e., β-amyloid (Aβ) and tau protein, leading to cell death. Several neuropeptides present in the central nervous system (CNS) are believed to be involved in the pathophysiology of AD. Among them, neuropeptide Y (NPY), a small peptide widely distributed throughout the brain, has generated interest because of its role in neuroprotection against excitotoxicity in animal models of AD. In addition, it has been shown that NPY modulates neurogenesis. Interestingly, these latter effects are similar to those elicited by neurotrophins, which are critical molecules for the function and survival of neurons that degenerate during the course of AD. In this review we summarize the evidence for the involvement of NPY and neurotrophins in AD pathogenesis, and the similarity between them in CNS neurons. Finally, we recapitulate our recent in-vitro evidence for the involvement of neurotrophin nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the neuroprotective effect elicited by NPY in AD neuron-like models (neuroblastoma cells or primary cultures exposed to toxic concentrations of Aβ's pathogenic fragment 25-35), and propose a putative mechanism based on NPY-induced inhibition of voltage-dependent Ca2+ influx in preand post-synaptic neurons.

Original languageEnglish
Pages (from-to)621-630
Number of pages10
JournalCanadian Journal of Physiology and Pharmacology
Volume92
Issue number8
DOIs
Publication statusPublished - 2014

Keywords

  • Alzheimer's disease
  • Amyloid β
  • Brain-derived neurotrophic factor
  • In vitro models
  • Nerve growth factor
  • Neuropeptide Y
  • Neuroprotection
  • Neurotrophins

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology
  • Medicine(all)

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