Dysregulation of the mTOR signaling pathway is associated with highly epileptogenic conditions such as tuberous sclerosis, focal cortical dysplasia, hemimegalencephaly and ganglioglioma, grouped under the term of 'mTORopathies'. Brain abnormalities associated with mTOR overactivation include enlarged and dysplastic neurons, abnormal cortical organization and astrogliosis. mTOR signaling intervenes in several molecular/biochemical processes leading to epileptogenesis. Animal models demonstrated that mTOR inhibitors could exert both an anticonvulsant action and an antiepileptogenic effect in models of genetic and acquired epilepsy. Preliminary studies in patients affected by tuberous sclerosis and treated with rapamycin or everolimus demonstrated potential benefits in seizure frequency reduction, suggesting that mTOR inhibition could be a promising treatment option for mTORopathies-related epilepsy. The authors reviewed the current knowledge of mTOR overactivation in different forms of epilepsy, and discuss the potential clinical use of mTOR inhibitors.

Curatolo, P., & Moavero, R. (2013). MTOR inhibitors as a new therapeutic option for epilepsy. EXPERT REVIEW NEUROTHERAPEUTICS, 13(6), 627-638 [10.1586/ern.13.49].

MTOR inhibitors as a new therapeutic option for epilepsy

CURATOLO, PAOLO;MOAVERO, ROMINA
2013

Abstract

Dysregulation of the mTOR signaling pathway is associated with highly epileptogenic conditions such as tuberous sclerosis, focal cortical dysplasia, hemimegalencephaly and ganglioglioma, grouped under the term of 'mTORopathies'. Brain abnormalities associated with mTOR overactivation include enlarged and dysplastic neurons, abnormal cortical organization and astrogliosis. mTOR signaling intervenes in several molecular/biochemical processes leading to epileptogenesis. Animal models demonstrated that mTOR inhibitors could exert both an anticonvulsant action and an antiepileptogenic effect in models of genetic and acquired epilepsy. Preliminary studies in patients affected by tuberous sclerosis and treated with rapamycin or everolimus demonstrated potential benefits in seizure frequency reduction, suggesting that mTOR inhibition could be a promising treatment option for mTORopathies-related epilepsy. The authors reviewed the current knowledge of mTOR overactivation in different forms of epilepsy, and discuss the potential clinical use of mTOR inhibitors.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/39 - Neuropsichiatria Infantile
eng
Con Impact Factor ISI
Animals; Anticonvulsants; Epilepsy; Humans; Immunosuppressive Agents; Signal Transduction; TOR Serine-Threonine Kinases
Curatolo, P., & Moavero, R. (2013). MTOR inhibitors as a new therapeutic option for epilepsy. EXPERT REVIEW NEUROTHERAPEUTICS, 13(6), 627-638 [10.1586/ern.13.49].
Curatolo, P; Moavero, R
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/133544
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