title: The effect of neuropeptide Y on cell survival and neurotrophin expression in in-vitro models of Alzheimer's disease.
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 Ca(2+) influx in pre- and post-synaptic neurons.
authors.affiliation: a Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Via Ardeatina 354, 00142 Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelucci
authors.forename: Francesca
authors.initials: F
authors.lastname: Gelfo
authors.forename: Marco
authors.initials: M
authors.lastname: Fiore
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Croce
authors.forename: Aleksander A
authors.initials: AA
authors.lastname: Mathé
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009478:Neuropeptide Y / Q000378:metabolism* / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D015220:Calcium Channels; D009414:Nerve Growth Factors; D009478:Neuropeptide Y; D018696:Neuroprotective Agents
keywords: Alzheimer’s disease; amyloid β; amyloïde β; brain-derived neurotrophic factor; facteur BNDF; facteur neuronal NGF; in vitro models; maladie d’Alzheimer; modèles in vitro; nerve growth factor; neuropeptide Y; neuroprotection; neurotrophines; neurotrophins