Guarana (Paullinia cupanaMart.) protects against amyloid-β toxicity inCaenorhabditis elegansthrough heat shock protein response activation

Alzheimer disease (AD) is a progressive neurodegenerative brain disorder that causes significant disruption in normal brain functioning, representing the most common cause of dementia in the elderly. The main hallmark of AD is the presence of amyloid plaques in the brain formed by the deposition of insoluble amyloid protein (A beta) outside of neurons. Despite intensive investigation of the mechanisms of AD pathogenesis during the past three decades, little has been achieved in terms of effective treatments or ways to prevent the disease.Paullinia cupana, known as guarana, is a plant endemic to the Amazon region in Brazil with several beneficial effects reported, including delayed aging. In this study, we investigated the effects of chronic consumption of guarana ethanolic extract (GEE) on A beta toxicity using aC. elegansmodel of AD. We analyzed the behavioral phenotype, oxidative damage and A beta protein expression in worms treated with GEE. In addition, we investigated the possible role of the heat shock response on the beneficial effects induced by GEE. Overall, our data demonstrate that chronic GEE treatment decreased the formation of A beta aggregates inC. elegans, preventing the behavioral deficits and the oxidative damage inducible by A beta expression, due to activation of the heat shock protein (HSP) response. This finding provides a new alternative against amyloidogenic neurodegenerative diseases and other diseases caused by protein accumulation during aging.