Diphenyl-diselenide suppresses amyloid-β peptide in Caenorhabditis elegans model of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common and devastating neurodegenerative disease. The etiology of AD has yet to be fully understood, and common treatments remain largely non-efficacious. The amyloid hypothesis posits that extracellular amyloid-β (Aβ) deposits are the fundamental etiological factor of the disease. The present study tested the organoselenium compound diphenyl-diselenide (PhSe)2, which is characterized by its antioxidant and antiinflammatory properties and has shown efficacy in several neurodegenerative disease models. We employed a transgenic Caenorhabditis elegans AD model to analyze the effects of (PhSe)2 treatment on Aβ peptide-induced toxicity. Chronic exposure to (PhSe)2 attenuated oxidative stress induced by Aβ1-42, with concomitant recovery of associative learning memory in C. elegans. Additionally, (PhSe)2 decreased Aβ1-42 transgene expression, suppressed Aβ1-42 peptide, and downregulated hsp-16.2 by reducing the need for this chaperone under Aβ1-42-induced toxicity. These observations suggest that (PhSe)2 plays an important role in protecting against oxidative stress-induced toxicity, thus representing a promising pharmaceutical modality that attenuates Aβ1-42 expression.

Keywords: Alzheimer’s disease; C. elegans; amyloid-β; neurodegenerative diseases; selenium compounds.