Guarana (Paullinia cupana Mart.) protects against amyloid-β toxicity in Caenorhabditis elegans through heat shock protein response activation

Abstract

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 (Aβ) 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 Aβ toxicity using a C. elegans model of AD. We analyzed the behavioral phenotype, oxidative damage and Aβ 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 Aβ aggregates in C. elegans, preventing the behavioral deficits and the oxidative damage inducible by Aβ 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.

GRAPHICAL ABSTRACT

Keywords:

• Neurodegenerative diseases
• Alzheimer’s
• proteostase
• natural compounds
• heat shock factor-1
• heat shock proteins

Acknowledgements

This working was supported by the Brazilian research funding agencies Instituto Nacional de Ciência e Tecnologia (INCT) for Excitotoxicity and Neuroprotection —MCT/CNPq, Programa de Apoio a Núcleos Emergentes (PRONEM/FAPERGS) 16/2551-0000248-7, CNPq, CAPES and PRAE/UFSM.

The authors are thankful to Prof. PhD Michael Aschner from Albert Einstein College of Medicine for kindly provide us the RNAi clones. We also thank the Caenorhabditis elegans Genetic Center (CGC) for provide the strains and the BioMed Proofreading LLC for editing the manuscript.

Conflict of interest None

Ethics approval None

ORCID

Daniele Coradini Zamberlan http://orcid.org/0000-0002-2040-3224

Marina Lopes Machado http://orcid.org/0000-0001-7425-3316

Félix Alexandre Antunes Soares http://orcid.org/0000-0002-6453-7902