Multiple Actions of H2S-Releasing Peptides in Human β-Amyloid Expressing C. elegans

ACS Chem Neurosci. 2022 Dec 7;13(23):3378-3388. doi: 10.1021/acschemneuro.2c00402. Epub 2022 Nov 9.

Abstract

Alzheimer's disease (AD) is a debilitating progressive neurodegenerative disorder characterized by the loss of cognitive function. A major challenge in treating this ailment fully is its multifactorial nature, as it is associated with effects like deposition of Aβ plaques, oxidative distress, inflammation of neuronal cells, and low levels of the neurotransmitter acetylcholine (ACh). In the present work, we demonstrate the design, synthesis, and biological activity of peptide conjugates by coupling a H2S-releasing moiety to the peptides known for their Aβ antiaggregating properties. These conjugates release H2S in a slow and sustained manner, due to the formation of self-assembled structures and delivered a significant amount of H2S within Caenorhabditis elegans. These conjugates are shown to target multiple factors responsible for the progression of AD: notably, we observed reduction in oxidative distress, inhibition of Aβ aggregation, and significantly increased ACh levels in the C. elegans model expressing human Aβ.

Keywords: Alzheimer’s disease; Aβ aggregation; acetylcholine; hydrogen sulfide; oxidative distress; peptides.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amyloid beta-Peptides*
  • Animals
  • Caenorhabditis elegans*
  • Humans

Substances

  • Amyloid beta-Peptides