Person:
Ramos Alonso, Eva

Profile Picture
First Name
Eva
Last Name
Ramos Alonso
URI
https://hdl.handle.net/20.500.14352/80441
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
Department
Farmacología y Toxicología
Area
Toxicología
Identifiers
UCM identifierORCIDScopus Author IDWeb of Science ResearcherIDDialnet ID

Filters

20232
Reset filters

Settings

Author: Egea, Javier × Subject: 615.1 ×

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Redox Regulation of Microglial Inflammatory Response: Fine Control of NLRP3 Inflammasome through Nrf2 and NOX4
    (Antioxidants, 2023) Palomino Antolín, Alejandra; Decouty-Pérez, Céline; Farré Alins, Víctor; Narros Fernández, Paloma; López Rodríguez, Ana Belén; Álvarez Rubal, María; Valencia, Inés; López Muñoz, Francisco; Ramos Alonso, Eva; Cuadrado, Antonio; Casas, Ana I.; Romero Martínez, Manuel Alejandro; Egea, Javier
    The role of inflammation and immunity in the pathomechanism of neurodegenerative diseases has become increasingly relevant within the past few years. In this context, the NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in the activation of inflammatory responses by promoting the maturation and secretion of pro-inflammatory cytokines such as interleukin-1β and interleukin-18. We hypothesized that the interplay between nuclear factor erythroid 2-related factor 2 (Nrf2) and NADPH oxidase 4 (NOX4) may play a critical role in the activation of the NLRP3 inflammasome and subsequent inflammatory responses. After priming mixed glial cultures with lipopolysaccharide (LPS), cells were stimulated with ATP, showing a significant reduction of IL1-β release in NOX4 and Nrf2 KO mice. Importantly, NOX4 inhibition using GKT136901 also reduced IL-1β release, as in NOX4 KO mixed glial cultures. Moreover, we measured NOX4 and NLRP3 expression in wild-type mixed glial cultures following LPS treatment, observing that both increased after TLR4 activation, while 24 h treatment with tert-butylhydroquinone, a potent Nrf2 inducer, significantly reduced NLRP3 expression. LPS administration resulted in significant cognitive impairment compared to the control group. Indeed, LPS also modified the expression of NLRP3 and NOX4 in mouse hippocampus. However, mice treated with GKT136901 after LPS impairment showed a significantly improved discrimination index and recovered the expression of inflammatory genes to normal levels compared with wild-type animals. Hence, we here validate NOX4 as a key player in NLRP3 inflammasome activation, suggesting NOX4 pharmacological inhibition as a potent therapeutic approach in neurodegenerative diseases.
  • Thumbnail Image
    Item
    Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging
    (Antioxidants, 2023) Jiménez Carretero, Victoria; Ramos Alonso, Eva; Segura Chama, Pedro; Hernández, Adan; Baraibar, Andrés M.; Álvarez Merz, Iris; López Muñoz, Francisco; Egea, Javier; Solís, José M.; Romero Martínez, Manuel Alejandro; Hernández Guijo, Jesús M.
    The aim of this review is to explore the relationship between melatonin, free radicals, and non-excitatory amino acids, and their role in stroke and aging. Melatonin has garnered significant attention in recent years due to its diverse physiological functions and potential therapeutic benefits by reducing oxidative stress, inflammation, and apoptosis. Melatonin has been found to mitigate ischemic brain damage caused by stroke. By scavenging free radicals and reducing oxidative damage, melatonin may help slow down the aging process and protect against age-related cognitive decline. Additionally, non-excitatory amino acids have been shown to possess neuroprotective properties, including antioxidant and anti-inflammatory in stroke and aging-related conditions. They can attenuate oxidative stress, modulate calcium homeostasis, and inhibit apoptosis, thereby safeguarding neurons against damage induced by stroke and aging processes. The intracellular accumulation of certain non-excitatory amino acids could promote harmful effects during hypoxia-ischemia episodes and thus, the blockade of the amino acid transporters involved in the process could be an alternative therapeutic strategy to reduce ischemic damage. On the other hand, the accumulation of free radicals, specifically mitochondrial reactive oxygen and nitrogen species, accelerates cellular senescence and contributes to age-related decline. Recent research suggests a complex interplay between melatonin, free radicals, and non-excitatory amino acids in stroke and aging. The neuroprotective actions of melatonin and non-excitatory amino acids converge on multiple pathways, including the regulation of calcium homeostasis, modulation of apoptosis, and reduction of inflammation. These mechanisms collectively contribute to the preservation of neuronal integrity and functions, making them promising targets for therapeutic interventions in stroke and age-related disorders.