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Andean medicinal plants and their secondary metabolites: Connections between Aymara traditional medicine and modern pharmacology
(Elsevier BV, 2025-03)
Ivania Cortés
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CERIC GARRIDO, FRANCISCO JOSE
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Hellen Navarrete
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Maité Rodríguez-Díaz
;
María Carolina Otero
Scopus© Citations 6 2
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Small molecules to perform big roles: The search for Parkinson's and Huntington's disease therapeutics
(2023)
Rodrigo Pérez-Arancibia
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Marisol Cisternas-Olmedo
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Denisse Sepúlveda
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Paulina Troncoso-Escudero
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Rene L. Vidal
<jats:p>Neurological motor disorders (NMDs) such as Parkinson's disease and Huntington's disease are characterized by the accumulation and aggregation of misfolded proteins that trigger cell death of specific neuronal populations in the central nervous system. Differential neuronal loss initiates the impaired motor control and cognitive function in the affected patients. Although major advances have been carried out to understand the molecular basis of these diseases, to date there are no treatments that can prevent, cure, or significantly delay the progression of the disease. In this context, strategies such as gene editing, cellular therapy, among others, have gained attention as they effectively reduce the load of toxic protein aggregates in different models of neurodegeneration. Nevertheless, these strategies are expensive and difficult to deliver into the patients' nervous system. Thus, small molecules and natural products that reduce protein aggregation levels are highly sought after. Numerous drug discovery efforts have analyzed large libraries of synthetic compounds for the treatment of different NMDs, with a few candidates reaching clinical trials. Moreover, the recognition of new druggable targets for NMDs has allowed the discovery of new small molecules that have demonstrated their efficacy in pre-clinical studies. It is also important to recognize the contribution of natural products to the discovery of new candidates that can prevent or cure NMDs. Additionally, the repurposing of drugs for the treatment of NMDs has gained huge attention as they have already been through clinical trials confirming their safety in humans, which can accelerate the development of new treatment. In this review, we will focus on the new advances in the discovery of small molecules for the treatment of Parkinson's and Huntington's disease. We will begin by discussing the available pharmacological treatments to modulate the progression of neurodegeneration and to alleviate the motor symptoms in these diseases. Then, we will analyze those small molecules that have reached or are currently under clinical trials, including natural products and repurposed drugs.</jats:p>
3Scopus© Citations 21
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Aspirin and N‐acetylcysteine co‐administration markedly inhibit chronic ethanol intake and block relapse binge drinking: Role of neuroinflammation‐oxidative stress self‐perpetuation
(2019)
Yedy Israel
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María Elena Quintanilla
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EZQUER, EDUARDO FERNANDO
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Paola Morales
;
Daniela Santapau
Scopus© Citations 34 2
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Editorial: Free Fatty Acids as Signaling Molecules: Role of Free Fatty Acid Receptors and CD36
(2022)
Carlos Puebla
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Eugenia Morselli
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Naim Akhtar Khan
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Mauricio A. Retamal
Scopus© Citations 6 1
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The Role of Colchicine in Atherosclerosis: From Bench to Bedside
(2022)
Leticia González
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Juan Francisco Bulnes
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María Paz Orellana
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MUÑOZ VENTURELLI, PAULA ANDREA
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Gonzalo Martínez Rodriguez
Inflammation is a key feature of atherosclerosis. The inflammatory process is involved in all stages of disease progression, from the early formation of plaque to its instability and disruption, leading to clinical events. This strongly suggests that the use of anti-inflammatory agents might improve both atherosclerosis progression and cardiovascular outcomes. Colchicine, an alkaloid derived from the flower Colchicum autumnale, has been used for years in the treatment of inflammatory pathologies, including Gout, Mediterranean Fever, and Pericarditis. Colchicine is known to act over microtubules, inducing depolymerization, and over the NLRP3 inflammasome, which might explain its known anti-inflammatory properties. Recent evidence has shown the therapeutic potential of colchicine in the management of atherosclerosis and its complications, with limited adverse effects. In this review, we summarize the current knowledge regarding colchicine mechanisms of action and pharmacokinetics, as well as the available evidence on the use of colchicine for the treatment of coronary artery disease, covering basic, translational, and clinical studies.
Scopus© Citations 27 1
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Protein kinase R is an innate immune sensor of proteotoxic stress via accumulation of cytoplasmic IL-24
(2022)
Sophia Davidson
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Chien-Hsiung Yu
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Annemarie Steiner
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Frédéric Ebstein
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Paul J. Baker
<jats:p>Proteasome dysfunction can lead to autoinflammatory disease associated with elevated type I interferon (IFN-αβ) and NF-κB signaling; however, the innate immune pathway driving this is currently unknown. Here, we identified protein kinase R (PKR) as an innate immune sensor for proteotoxic stress. PKR activation was observed in cellular models of decreased proteasome function and in multiple cell types from patients with proteasome-associated autoinflammatory disease (PRAAS). Furthermore, genetic deletion or small-molecule inhibition of PKR in vitro ameliorated inflammation driven by proteasome deficiency. In vivo, proteasome inhibitor–induced inflammatory gene transcription was blunted in PKR-deficient mice compared with littermate controls. PKR also acted as a rheostat for proteotoxic stress by triggering phosphorylation of eIF2α, which can prevent the translation of new proteins to restore homeostasis. Although traditionally known as a sensor of RNA, under conditions of proteasome dysfunction, PKR sensed the cytoplasmic accumulation of a known interactor, interleukin-24 (IL-24). When misfolded IL-24 egress into the cytosol was blocked by inhibition of the endoplasmic reticulum–associated degradation pathway, PKR activation and subsequent inflammatory signaling were blunted. Cytokines such as IL-24 are normally secreted from cells; therefore, cytoplasmic accumulation of IL-24 represents an internal danger-associated molecular pattern. Thus, we have identified a mechanism by which proteotoxic stress is detected, causing inflammation observed in the disease PRAAS.</jats:p>
Scopus© Citations 55 3
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Use of Corticosteroids in COVID-19
(2020)
ROESSLER VERGARA, PATRICIA ANDREA
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Gigia Roizen
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IBAÑEZ, SEBASTIAN
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VALENZUELA LETELIER, OMAR ANTONIO
1Scopus© Citations 1 1
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N-Acetylcysteine and Acetylsalicylic Acid Inhibit Alcohol Consumption by Different Mechanisms: Combined Protection
(2020)
María Elena Quintanilla
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EZQUER, EDUARDO FERNANDO
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Paola Morales
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EZQUER, EDUARDO MARCELO
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OLIVARES, MARIA BELEN
Scopus© Citations 21 1
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Activated mesenchymal stem cell administration inhibits chronic alcohol drinking and suppresses relapse-like drinking in high-alcohol drinker rats
(2019)
EZQUER, EDUARDO FERNANDO
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María Elena Quintanilla
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Paola Morales
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EZQUER, EDUARDO MARCELO
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Carolyne Lespay-Rebolledo
1Scopus© Citations 31 2
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Intranasal mesenchymal stem cell secretome administration markedly inhibits alcohol and nicotine self-administration and blocks relapse-intake: mechanism and translational options
(2019)
María Elena Quintanilla
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EZQUER, EDUARDO FERNANDO
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Paola Morales
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Daniela Santapau
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BERRIOS CARCAMO, PABLO ANDRES
14Scopus© Citations 28

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