Echeverry López, Carolina

Research interests

Throughout my academic career, my main research lines have focused on studying the biochemical and molecular mechanisms leading to neuronal death in in vitro and in vivo experimental models, as well as the search for new therapeutic agents of natural origin.
At the beginning of my academic training, between 1998 and 2004, in collaboration with the National Institute of Viticulture (INAVI), we investigated the antioxidant capacity of national red wines, their relationship with polyphenolic composition, and different aspects of their production and vinification. As part of this research line, I completed my Master's studies in Biotechnology (2002, Faculty of Sciences, UdelaR), during which we described for the first time the analytical, production, and biological activity aspects of Uruguayan wines (Echeverry et al., 2004; Echeverry et al., 2005). In parallel, we investigated the cytoprotective capacity of flavonoid compounds (some of which are present in wine) in in vitro models of neuronal death using cell cultures, as well as in vivo experimental models of hypoxia and ischemia.
In 2007, in collaboration with the Department of Chemistry at the University of Nairobi, Kenya, and supported by the Organization for the Prohibition of Chemical Weapons (OPCW), we investigated the relationship between the molecular structure of natural flavones and neuroprotection in cell cultures. The results confirmed that the structural requirements for neuronal protection differ from those required for antioxidant properties, identifying a neuroprotective pharmacophore in flavones (Echeverry et al., 2010). These findings were part of my Ph.D. studies (2015, PEDECIBA Biology), whose results were published in several research articles, reviews, and book chapters (Echeverry et al., 2015; Dajas et al., 2015, 2013; Arredondo et al., 2015).

In 2017, I began researching the therapeutic potential of cannabinoids and cannabis extracts for medical use. In collaboration with Dr. Scorza's group (Department of Experimental Neuropharmacology at IIBCE), we determined the neuroprotective capacity of two non-psychotomimetic cannabinoid compounds: cannabidiol (CBD) and cannabigerol (CBG), leading to an original research publication (Echeverry et al., 2021), a review on the chemical composition of cannabis (Echeverry et al., 2021), and a book chapter on the mechanisms of action of CBD and CBG (Echeverry et al., 2023; book: Medicinal Usage of Cannabis and Cannabinoids).
Furthermore, through the Fondo Clemente Estable project "Medicinal Use of Cannabinoids: Searching for a THC:CBD or THC:CBG Combination to Enhance Their Neuroprotective Action and Improve Their Brain Bioavailability," we demonstrated that in primary cultures of cerebellar granule neurons exposed to rotenone, there is no neuroprotective synergy between CBD, CBG, and THC, suggesting that these three cannabinoids act through similar mechanisms. Recently, we found that Sigma1 receptor activation by CBD is responsible for its neuroprotective action in this model, suggesting a novel target for CBD (article in preparation).Additionally, we advanced in studying the neuroprotective properties of two medical cannabis extracts: a full-spectrum pharmaceutical-grade extract (Epifractán) and a purified CBD extract (Xalex), both prepared in the same formulation vehicle (MCT, medium-chain triglyceride). Our recent publication demonstrated that the neuroprotective effect of these products is due to their CBD content and that the formulation vehicle (MCT) is crucial, as it eliminates CBD toxicity at high concentrations (Echeverry et al., 2023). We are currently studying the brain availability of an intranasal CBD-MCT formulation (article in preparation).

Since neurodegenerative and neuropsychiatric disorders share common features such as degenerative and inflammatory processes, I was invited to join the research team of an ANII-funded project (FCE_1_2021_1_166638), which aims to evaluate the role of the adenosine transporter ENT1 in the therapeutic potential of cannabidiol for stimulant use disorder.
From its inception in 2019 until 2023, I was part of the CYTED CannaLatan Network "Development of Cannabinoids for the Treatment of Neurodegenerative Diseases," collaborating with researchers from Spain, Mexico, Brazil, Argentina, Bolivia, and Uruguay.
During this time, I also remained actively involved in other laboratory research lines focused on polyphenols as therapeutic strategies, co-authoring two published articles (Martínez et al., 2019; Santi et al., 2020). In this field, I served as the scientific lead at IIBCE for the Alianza project (ALI_2_2018_1_149574) "Generation of Polyphenol-Rich Extracts from Grape Pomace," which was recently completed.
Currently, I am part of the research team in two recently approved ANII projects (FCE-2024 and FMV-2024) and another CABBIO project (2024), all focused on investigating natural products as neuroprotective agents

Working area

Medical and Health Sciences / Basic Medicine / Neurosciences / Neurochemistry; Neuropharmacology; Cellular Mechanisms of Neurodegeneration and Neuroprotection; Therapeutic Properties of Natural Products; Structure-Activity Relationship of Natural Compounds; Medicinal Use of Cannabis and Cannabinoids