Vías de señalización mTOR y AKT en epilepsia

Romero-Leguizamón, C R; Ramirez-Latorre, J.; Mora-Muñóz, Laura; Guerrero-Naranjo, Alejandro

doi:10.33588/rn.6301.2015459

Cited by 5 publications

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“…Recent studies have suggested that a variety of signaling pathways may be associated with epilepsy ( 54 ). These pathways include the Phosphatidylinositol-3-kinase (PI3K) / protein kinase B (Akt) / mammalian target of rapamycin (mTOR) signaling pathway that regulates the autophagy process in neurodegenerative diseases ( 55 ), the Wnt/β-catenin signaling pathway ( 56 ), mitogen-activated protein kinase (MAPK) signaling pathway ( 57 ) and the TLR4/ NF-κB pathway ( 58 ) that is associated with neurogenesis and neuronal death. Different inflammatory factors are closely related to these signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice

et al. 2022

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Sodium valproate (VPA) is a broad-spectrum anticonvulsant that is effective both in adults and children suffering from epilepsy, but it causes psychiatric and behavioral side effects in patients with epilepsy. In addition, 30% of patients with epilepsy develop resistance to VPA. At present, regular physical exercise has shown many benefits and has become an effective complementary therapy for various brain diseases, including epilepsy. Therefore, we wondered whether VPA combined with exercise would be more effective in the treatment of seizures and associated co-morbidities. Here, we used a mouse model with kainic acid (KA)-induced epilepsy to compare the seizure status and the levels of related co-morbidities, such as cognition, depression, anxiety, and movement disorders, in each group using animal behavioral experiment and local field potential recordings. Subsequently, we investigated the mechanism behind this phenomenon by immunological means. Our results showed that low-intensity exercise combined with VPA reduced seizures and associated co-morbidities. This phenomenon seems to be related to the Toll-like receptor 4, activation of the nuclear factor kappa B (NF-κB), and release of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and IL-6. In brief, low-intensity exercise combined with VPA enhanced the downregulation of NF-κB-related inflammatory response, thereby alleviating the seizures, and associated co-morbidities.

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Section: Discussionmentioning

confidence: 99%

Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice

et al. 2022

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“…7 El primer golpe, que induce una MDC, tiene una naturaleza genética, la cual se ha relacionado con la vía mTOR (blanco de la rapamicina en mamíferos o mammalian target of rapamycin, por sus siglas en inglés). [8][9][10] El segundo golpe puede ser una segunda mutación o una lesión adquirida, por ejemplo, un traumatismo craneoencefálico. 11,12 La vía de señalización mTOR es un eje de los procesos de regulación celular y estas alteraciones tienen un papel fisiopatológico en enfermedades neurológicas como la esclerosis tuberosa, las MDC, los espasmos infantiles, el estado epiléptico y las secuelas del daño cerebral traumático.…”

Section: Wwwmedigraphicorgmxunclassified

“…11,12 La vía de señalización mTOR es un eje de los procesos de regulación celular y estas alteraciones tienen un papel fisiopatológico en enfermedades neurológicas como la esclerosis tuberosa, las MDC, los espasmos infantiles, el estado epiléptico y las secuelas del daño cerebral traumático. [8][9][10] La mTOR es una serina treonincinasa que constituye el núcleo de una red compleja de señalización intracelular, la cual reconoce una amplia variedad de señales ambientales y, en consecuencia, regula funciones celulares tales como el crecimiento, la proliferación, la supervivencia y el metabolismo.…”

Section: Wwwmedigraphicorgmxunclassified

“…Estos complejos comparten la subunidad cinasa mTOR y a un componente proteico Deptor, el cual es inhibidor de la actividad mTOR. [8][9][10] Cada uno de estos dos complejos contiene sitios de acoplamiento particulares que modulan la acción de la enzima. La rapamicina actúa sobre el complejo mTORC1, inhibiéndolo.…”

Section: Wwwmedigraphicorgmxunclassified

“…[8][9][10] La rapamicina o sirolimus es un macrólido derivado de la bacteria Streptomyces hygroscopicus, cuya actividad antifúngica e inmunosupresora se describió primero; posteriormente, se caracterizaron sus propiedades inhibitorias sobre mTOR. 8 El objetivo de este reporte es revisar el seguimiento de un paciente con una MCD hemisférica compleja, la cual se manifiesta como una epilepsia con crisis focales con alteración de la conciencia y bilateralización secundaria. Analizar la teoría del «doble golpe», esto es, «primero y segundo golpe» en relación con la epilepsia y MDC, a propósito de este reporte de caso.…”

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Malformación del desarrollo cortical hemisférico

Figueroa¹,

Berzabá²,

Navarrete³

2020

Anales Médicos De La Asociación Médica Del Centro Médico ABC

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Resveratrol Activates Autophagy via the AKT/mTOR Signaling Pathway to Improve Cognitive Dysfunction in Rats With Chronic Cerebral Hypoperfusion

Wang¹,

He²,

Pan³

et al. 2019

Front. Neurosci.

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Chronic cerebral hypoperfusion (CCH) is a main cause of vascular dementia and is also an etiological factor of neurological diseases and mental disorders. However, few treatments are available for CCH, and new medications are needed. In the present study, we employed a rat model of CCH that was based on bilateral common carotid artery occlusion and investigated the therapeutic effects of resveratrol and its detailed mechanism of action. We evaluated neurological deficit scores and performed the Morris water maze test, hematoxylin and eosin staining, TUNEL staining, enzyme-linked immunosorbent assays, and Western blot. Resveratrol reduced neurological deficit scores in CCH rats and reduced pathological damage in the frontal cortex and hippocampus. Resveratrol activated autophagy and inhibited the expression of AKT/mechanistic target of rapamycin (mTOR) signaling pathway-related proteins. Treatment with a phosphoinositide-3 kinase inhibitor reversed the protective effect of resveratrol. These findings suggest that resveratrol improves cognitive function in a rat model of CCH and reduces oxidative stress-induced neuronal damage in the frontal cortex and hippocampus by activating autophagy and inhibiting neuronal apoptosis. These effects may be regulated by the AKT/mTOR signaling pathway.

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Vías de señalización mTOR y AKT en epilepsia

Cited by 5 publications

References 0 publications

Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice

Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice

Malformación del desarrollo cortical hemisférico

Resveratrol Activates Autophagy via the AKT/mTOR Signaling Pathway to Improve Cognitive Dysfunction in Rats With Chronic Cerebral Hypoperfusion

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