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Although previous studies have indicated that guarana has some protective effects in Parkinson\u2019s (PD), Alzheimer\u2019s (AD), and Huntington\u2019s (HD) disease models, the underlying mechanisms are unknown. Here, we investigated the protective effects of guarana hydroalcoholic extract (GHE) in <jats:italic>Caenorhabditis elegans<\/jats:italic> models of HD and AD. GHE reduced polyglutamine (polyQ) protein aggregation in the muscle and also reduced polyQ\u2010mediated neuronal death in ASH sensory neurons and delayed <jats:italic>\u03b2<\/jats:italic>\u2010amyloid\u2010induced paralysis in a caffeine\u2010independent manner. Moreover, GHE\u2019s protective effects were not mediated by caloric restriction, antimicrobial effects, or development and reproduction impairment. Inactivation of the transcription factors SKN\u20101 and DAF\u201016 by RNAi partially blocked the protective effects of GHE treatment in the AD model. We show that the protective effect of GHE is associated with antioxidant activity and modulation of proteostasis, since it increased the lifespan and proteasome activity, reduced intracellular ROS and the accumulation of autophagosomes, and increased the expression of SOD\u20103 and HSP\u201016.2. Our findings suggest that GHE has therapeutic potential in combating age\u2010related diseases associated with protein misfolding and accumulation.<\/jats:p>","DOI":"10.1155\/2018\/9241308","type":"journal-article","created":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T23:38:28Z","timestamp":1530747508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Guarana (<i>Paullinia cupana<\/i>) Extract Protects <i>Caenorhabditis elegans<\/i> Models for Alzheimer Disease and Huntington Disease through Activation of Antioxidant and Protein Degradation Pathways"],"prefix":"10.1155","volume":"2018","author":[{"given":"Patr\u00edcia Ferreira","family":"Boasqu\u00edvis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna Melo Martins","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franciny 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