Neuroprotective effect of neuropeptide Y against β-amyloid 25-35 toxicity in SH-SY5Y neuroblastoma cells is associated with increased neurotrophin production.

Background: In the central nervous system, several neuropeptides are believed to be involved in the pathophysiology of Alzheimer's disease (AD). Among them, neuropeptide Y (NPY) is a small peptide widely distributed throughout the brain, where it serves as a neurotransmitter and/or a modulator of several neuroendocrine functions. More recently, NPY has generated interest because of its role in neuroprotection against excitotoxicity and modulation of neurogenesis. Interestingly, these effects are also influenced by neurotrophins, critical molecules for the function and survival of neurons that degenerate in AD.

Objective: Our purpose was to investigate whether NPY might be a neuroprotective agent in AD and whether neurotrophins are involved in NPY-induced neuroprotection.

Methods: To test this hypothesis, we exposed the SH-SY5Y neuroblastoma cell line to toxic concentrations of β-amyloid (Aβ) peptide fragment 25-35 (Aβ(25-35)) and measured cell survival and neurotrophin expression before and after a preincubation with NPY in the growth medium.

Results: Our results demonstrated that preincubation with NPY prevented cell loss due to the toxic effect of Aβ(25-35). Moreover, while intracellular production of nerve growth factor and brain-derived neurotrophic factor were reduced by Aβ, NPY restored or even increased neurotrophin protein and mRNA in SH-SY5Y cells.

Conclusion: In conclusion, this study demonstrates that NPY increases the survival of SH-SY5Y neuroblastoma cells and counteracts the toxic effect of Aβ. In addition, NPY restores the neurotrophin levels in these cells. Although preliminary, these observations might be useful to understand the pathology of Alzheimer's and/or develop new therapeutic strategies.