Kisspeptin prevention of Amyloid-? Peptide neurotoxicity in vitro

Milton, Nathaniel G.N., Chilumuri, Amrutha, Rocha-Ferreira, Eridan, Nercessian, Amanda N. and Ashioti, Maria (2012) Kisspeptin prevention of Amyloid-? Peptide neurotoxicity in vitro. ACS chemical neuroscience, 3 (9). pp. 706-719. ISSN 1948-7193

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Alzheimer’s disease (AD) onset is associated with changes in hypothalamic-pituitary–gonadal (HPG) function. The 54 amino acid kisspeptin (KP) peptide regulates the HPG axis and alters antioxidant enzyme expression. The Alzheimer’s amyloid-? (A?) is neurotoxic, and this action can be prevented by the antioxidant enzyme catalase. Here, we examined the effects of KP peptides on the neurotoxicity of A?, prion protein (PrP), and amylin (IAPP) peptides. The A?, PrP, and IAPP peptides stimulated the release of KP and KP 45–54. The KP peptides inhibited the neurotoxicity of A?, PrP, and IAPP peptides, via an action that could not be blocked by kisspeptin-receptor (GPR-54) or neuropeptide FF (NPFF) receptor antagonists. Knockdown of KiSS-1 gene, which encodes the KP peptides, in human neuronal SH-SY5Y cells with siRNA enhanced the toxicity of amyloid peptides, while KiSS-1 overexpression was neuroprotective. A comparison of the catalase and KP sequences identified a similarity between KP residues 42–51 and the region of catalase that binds A?. The KP peptides containing residues 45–50 bound A?, PrP, and IAPP, inhibited Congo red binding, and were neuroprotective. These results suggest that KP peptides are neuroprotective against A?, IAPP, and PrP peptides via a receptor independent action involving direct binding to the amyloid peptides.

Item Type: Article
Subjects: University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)
Depositing User: Rachel Wheelhouse
Date Deposited: 18 Oct 2012 09:04
Last Modified: 18 Jun 2013 09:09

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