Kisspeptin prevention of amyloid-β peptide neurotoxicity in vitro

Nathaniel G.N. Milton, Amrutha Chilumuri, Eridan Rocha-Ferreira, Amanda N. Nercessian, Maria Ashioti

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

Alzheimers 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 Alzheimers amyloid-β (Aβ) 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 Aβ, prion protein (PrP), and amylin (IAPP) peptides. The Aβ, PrP, and IAPP peptides stimulated the release of KP and KP 45-54. The KP peptides inhibited the neurotoxicity of Aβ, 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 Aβ. The KP peptides containing residues 45-50 bound Aβ, PrP, and IAPP, inhibited Congo red binding, and were neuroprotective. These results suggest that KP peptides are neuroprotective against Aβ, IAPP, and PrP peptides via a receptor independent action involving direct binding to the amyloid peptides.

Original languageEnglish
Pages (from-to)706-719
Number of pages14
JournalACS Chemical Neuroscience
Volume3
Issue number9
DOIs
Publication statusPublished - 19 Sep 2012
Externally publishedYes

Keywords

  • amylin
  • amyloid-β
  • KiSS-1
  • kisspeptin
  • neuroprotection
  • prion protein

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