Chen, Z., Brodie, M. J., Ding, D. & Kwan, P. Editorial: epidemiology of epilepsy and seizures. Front. Epidemiol. 3, 1273163 (2023).
Article PubMed PubMed Central Google Scholar
Devinsky, O. et al. Epilepsy. Nat. Rev. Dis. Prim. 4, 18024 (2018).
Scheffer, I. E. et al. ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology. Epilepsia 58, 512–521 (2017).
Article PubMed PubMed Central Google Scholar
Pitkanen, A., Lukasiuk, K., Dudek, F. E. & Staley, K. J. Epileptogenesis. Cold Spring Harb. Perspect. Med. 5, a022822 (2015).
Article PubMed PubMed Central Google Scholar
Galanopoulou, A. S. et al. Antiepileptogenesis and disease modification: progress, challenges, and the path forward — Report of the Preclinical Working Group of the 2018 NINDS-sponsored antiepileptogenesis and disease modification workshop. Epilepsia Open 6, 276–296 (2021).
Article PubMed PubMed Central Google Scholar
Curatolo, P., Moavero, R., van Scheppingen, J. & Aronica, E. mTOR dysregulation and tuberous sclerosis-related epilepsy. Exp. Rev. Neurother. 18, 185–201 (2018).
Vezzani, A., Balosso, S. & Ravizza, T. Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy. Nat. Rev. Neurol. 15, 459–472 (2019). This review describes inflammatory pathways that are activated in pharmaco-resistant epilepsy and can be modulated in animal models to produce therapeutic effects.
Article CAS PubMed Google Scholar
Aronica, E., Specchio, N., Luinenburg, M. J. & Curatolo, P. Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy. Brain 146, 2694–2710 (2023). This review provides an overview of the different biological mechanisms throughout the life course, even beyond the epileptogenic process, in individuals with tuberous sclerosis complex.
Article PubMed PubMed Central Google Scholar
Weichhart, T., Hengstschläger, M. & Linke, M. Regulation of innate immune cell function by mTOR. Nat. Rev. Immunol. 15, 599–614 (2015).
Article CAS PubMed PubMed Central Google Scholar
Klein, P. et al. Commonalities in epileptogenic processes from different acute brain insults: do they translate? Epilepsia 59, 37–66 (2018).
Article CAS PubMed Google Scholar
McDaniel, S. S., Rensing, N. R., Thio, L. L., Yamada, K. A. & Wong, M. The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway. Epilepsia 52, e7–e11 (2011).
Article CAS PubMed PubMed Central Google Scholar
Simeone, T. A., Simeone, K. A. & Rho, J. M. Ketone bodies as anti-seizure agents. Neurochem. Res. 42, 2011–2018 (2017).
Article CAS PubMed PubMed Central Google Scholar
Girodengo, M., Ultanir, S. K. & Bateman, J. M. Mechanistic target of rapamycin signaling in human nervous system development and disease. Front. Mol. Neurosci. 15, 1005631 (2022).
Article CAS PubMed PubMed Central Google Scholar
Saxton, R. A. & Sabatini, D. M. mTOR signaling in growth, metabolism, and disease. Cell 168, 960–976 (2017).
Article CAS PubMed PubMed Central Google Scholar
Andrews, M. G., Subramanian, L. & Kriegstein, A. R. mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex. eLife 9, e58737 (2020).
Article CAS PubMed PubMed Central Google Scholar
Rostamzadeh, D. et al. mTOR signaling pathway as a master regulator of memory CD8+ T-cells, Th17, and NK cells development and their functional properties. J. Cell Physiol. 234, 12353–12368 (2019).
Article CAS PubMed Google Scholar
Mühlebner, A., Bongaarts, A., Sarnat, H. B., Scholl, T. & Aronica, E. New insights into a spectrum of developmental malformations related to mTOR dysregulations: challenges and perspectives. J. Anat. 235, 521–542 (2019).
Article PubMed PubMed Central Google Scholar
Gerasimenko, A., Baldassari, S. & Baulac, S. mTOR pathway: insights into an established pathway for brain mosaicism in epilepsy. Neurobiol. Dis. 182, 106144 (2023).
Article CAS PubMed Google Scholar
Okoh, J. et al. Targeted suppression of mTORC2 reduces seizures across models of epilepsy. Nat. Commun. 14, 7364 (2023).
Article CAS PubMed PubMed Central Google Scholar
Hodges, S. L. & Lugo, J. N. Therapeutic role of targeting mTOR signaling and neuroinflammation in epilepsy. Epilepsy Res. 161, 106282 (2020).
Article CAS PubMed PubMed Central Google Scholar
Xiao, Z., Peng, J., Gan, N., Arafat, A. & Yin, F. Interleukin-1β plays a pivotal role via the PI3K/Akt/mTOR signaling pathway in the chronicity of mesial temporal lobe epilepsy. Neuroimmunomodulation 23, 332–344 (2016).
Article CAS PubMed Google Scholar
Switon, K., Kotulska, K., Janusz-Kaminska, A., Zmorzynska, J. & Jaworski, J. Molecular neurobiology of mTOR. Neuroscience 341, 112–153 (2017).
Article CAS PubMed Google Scholar
Fernandes, S. A. & Demetriades, C. The multifaceted role of nutrient sensing and mTORC1 signaling in physiology and aging. Front Aging 2, 707372 (2021).
Article PubMed PubMed Central Google Scholar
Zimmer, T. S. et al. Tuberous sclerosis complex as disease model for investigating mTOR-related gliopathy during epileptogenesis. Front. Neurol. 11, 1028 (2020).
Article PubMed PubMed Central Google Scholar
Figlia, G., Gerber, D. & Suter, U. Myelination and mTOR. Glia 66, 693–707 (2018).
Galanopoulou, A. S., Gorter, J. A. & Cepeda, C. Finding a better drug for epilepsy: the mTOR pathway as an antiepileptogenic target. Epilepsia 53, 1119–1130 (2012).
Article CAS PubMed PubMed Central Google Scholar
Curatolo, P., Specchio, N. & Aronica, E. Advances in the genetics and neuropathology of tuberous sclerosis complex: edging closer to targeted therapy. Lancet Neurol. 21, 843–856 (2022).
Article CAS PubMed Google Scholar
Najm, I. et al. The ILAE consensus classification of focal cortical dysplasia: an update proposed by an ad hoc task force of the ILAE diagnostic methods commission. Epilepsia 63, 1899–1919 (2022).
Article CAS PubMed PubMed Central Google Scholar
Nguyen, L. H. & Bordey, A. Current review in basic science: animal models of focal cortical dysplasia and epilepsy. Epilepsy Curr. 22, 234–240 (2022).
Article PubMed PubMed Central Google Scholar
Eichmüller, O. L. et al. Amplification of human interneuron progenitors promotes brain tumors and neurological defects. Science 375, eabf5546 (2022).
Article PubMed PubMed Central Google Scholar
Moavero, R. et al. Genetic pathogenesis of the epileptogenic lesions in tuberous sclerosis complex: therapeutic targeting of the mTOR pathway. Epilepsy Behav. 131, 107713 (2022).
Bockaert, J. & Marin, P. mTOR in brain physiology and pathologies. Physiol. Rev. 95, 1157–1187 (2015).
Article CAS PubMed Google Scholar
Talos, D. M. et al. Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy. Ann. Neurol. 83, 311–327 (2018).
Article CAS PubMed PubMed Central Google Scholar
Campolo, M. et al. The inhibition of mammalian target of rapamycin (mTOR) in improving inflammatory response after traumatic brain injury. J. Cell Mol. Med. 25, 7855–7866 (2021). This study shows that treatment with mTOR inhibitors ameliorated the neuroinflammation associated with traumatic brain injury showing a diminished neuronal death and astrogliosis after trauma.
Article CAS PubMed PubMed Central Google Scholar
Movahedpour, A. et al. Mammalian target of rapamycin (mTOR) signaling pathway and traumatic brain injury: a novel insight into targeted therapy. Cell Biochem. Funct. 40, 232–247 (2022).
Article CAS PubMed Google Scholar
Guo, D., Zeng, L., Brody, D. L. & Wong, M. Rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury. PLoS ONE 8, e64078 (2013). This study provides evidence that rapamycin treatment for 1 month after traumatic brain injury decreased the seizure frequency and rate of developing post-traumatic epilepsy, showing inhibition of epileptogenesis.
Comments (0)