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

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 Afi' 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 Afi' 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 Afi' aggregation, and significantly increased ACh levels in the C. elegans model expressing human Afi'.

Automated summary

This study demonstrates the design, synthesis, and biological activity of peptide conjugates that release H2S and possess anti-Alzheimer's disease properties. The conjugates target multiple factors involved in the progression of AD, including inhibition of aggregation, reduction of oxidative stress, and increased levels of ACh.