Table of Contents
ISRN Neuroscience
Volume 2013, Article ID 253210, 14 pages
Research Article

The Role of Neurotransmitters in Protection against Amyloid-β Toxicity by KiSS-1 Overexpression in SH-SY5Y Neurons

1Department of Human and Health Sciences, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK
2Health Sciences Research Centre, University of Roehampton, Holybourne Avenue, London SW15 4JD, UK

Received 17 May 2013; Accepted 19 June 2013

Academic Editors: S. V. Meethal and W. Portillo

Copyright © 2013 Amrutha Chilumuri and Nathaniel G. N. Milton. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Recent studies have suggested that the kisspeptin (KP) and kissorphin (KSO) peptides have neuroprotective actions against the Alzheimer’s amyloid-β (Aβ) peptide. Overexpression of the human KiSS-1 gene that codes for KP and KSO peptides in SH-SY5Y neurons has also been shown to inhibit Aβ neurotoxicity. The in vivo actions of KP include activation of neuroendocrine and neurotransmitter systems. The present study used antagonists of KP, neuropeptide FF (NPFF), opioids, oxytocin, estrogen, adrenergic, cholinergic, dopaminergic, serotonergic, and γ-aminobutyric acid (GABA) receptors plus inhibitors of catalase, cyclooxygenase, nitric oxide synthase, and the mitogen activated protein kinase cascade to characterize the KiSS-1 gene overexpression neuroprotection against Aβ cell model. The results showed that KiSS-1 overexpression is neuroprotective against Aβ and the action appears to involve the KP or KSO peptide products of KiSS-1 processing. The mechanism of neuroprotection does not involve the activation of the KP or NPFF receptors. Opioids play a role in the toxicity of Aβ in the KiSS-1 overexpression system and opioid antagonists naloxone or naltrexone inhibited Aβ toxicity. The mechanism of KiSS-1 overexpression induced protection against Aβ appears to have an oxytocin plus a cyclooxygenase dependent component, with the oxytocin antagonist atosiban and the cyclooxygenase inhibitor SC-560 both enhancing the toxicity of Aβ.