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Volume 12
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Review

Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging

by
Victoria Jiménez Carretero
1,
Eva Ramos
2,
Pedro Segura-Chama
3,
Adan Hernández
4,
Andrés M Baraibar
5,
Iris Álvarez-Merz
1,
Francisco López Muñoz
6,7,
Javier Egea
8,
José M. Solís
9,
Alejandro Romero
2 and
Jesús M. Hernández-Guijo
1,10,*
1
Department of Pharmacology and Therapeutic, Teófilo Hernando Institute, Faculty of Medicine, Universidad Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029 Madrid, Spain
2
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain
3
Investigador por México-CONAHCYT, Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”, Calzada México-Xochimilco 101, Huipulco, Tlalpan, Mexico City 14370, Mexico
4
Institute of Neurobiology, Universidad Nacional Autónoma of México, Juriquilla, Santiago de Querétaro 76230, Querétaro, Mexico
5
Department of Neurosciences, Universidad del País Vasco UPV/EHU, Achucarro Basque Center for Neuroscience, Barrio Sarriena, s/n, 48940 Leioa, Spain
6
Faculty of Health Sciences, University Camilo José Cela, C/Castillo de Alarcón 49, Villanueva de la Cañada, 28692 Madrid, Spain
7
Neuropsychopharmacology Unit, Hospital 12 de Octubre Research Institute (i + 12), Avda. Córdoba, s/n, 28041 Madrid, Spain
8
Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Health Research Institute, Hospital Universitario de la Princesa, 28006 Madrid, Spain
9
Neurobiology-Research Service, Hospital Ramón y Cajal, Carretera de Colmenar Viejo, Km. 9, 28029 Madrid, Spain
10
Ramón y Cajal Institute for Health Research (IRYCIS), Hospital Ramón y Cajal, Carretera de Colmenar Viejo, Km. 9, 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Antioxidants 2023, 12(10), 1844; https://doi.org/10.3390/antiox12101844
Submission received: 5 September 2023 / Revised: 23 September 2023 / Accepted: 26 September 2023 / Published: 10 October 2023
(This article belongs to the Special Issue Melatonin Metabolism and Aging)
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Abstract

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.
Keywords: melatonin; non-excitatory amino acids; free radicals; stroke; aging melatonin; non-excitatory amino acids; free radicals; stroke; aging

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MDPI and ACS Style

Carretero, V.J.; Ramos, E.; Segura-Chama, P.; Hernández, A.; Baraibar, A.M.; Álvarez-Merz, I.; Muñoz, F.L.; Egea, J.; Solís, J.M.; Romero, A.; et al. Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging. Antioxidants 2023, 12, 1844. https://doi.org/10.3390/antiox12101844

AMA Style

Carretero VJ, Ramos E, Segura-Chama P, Hernández A, Baraibar AM, Álvarez-Merz I, Muñoz FL, Egea J, Solís JM, Romero A, et al. Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging. Antioxidants. 2023; 12(10):1844. https://doi.org/10.3390/antiox12101844

Chicago/Turabian Style

Carretero, Victoria Jiménez, Eva Ramos, Pedro Segura-Chama, Adan Hernández, Andrés M Baraibar, Iris Álvarez-Merz, Francisco López Muñoz, Javier Egea, José M. Solís, Alejandro Romero, and et al. 2023. "Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging" Antioxidants 12, no. 10: 1844. https://doi.org/10.3390/antiox12101844

APA Style

Carretero, V. J., Ramos, E., Segura-Chama, P., Hernández, A., Baraibar, A. M., Álvarez-Merz, I., Muñoz, F. L., Egea, J., Solís, J. M., Romero, A., & Hernández-Guijo, J. M. (2023). Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging. Antioxidants, 12(10), 1844. https://doi.org/10.3390/antiox12101844

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