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mTOR pathway inhibition as a new therapeutic strategy in epilepsy and epileptogenesis.

Citraro, R; Leo, A; Constanti, A; Russo, E; Sarro, G; (2016) mTOR pathway inhibition as a new therapeutic strategy in epilepsy and epileptogenesis. Pharmacological Research , 107 10.1016/j.phrs.2016.03.039. Green open access

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Abstract

Several preclinical and some clinical studies have revealed that the mammalian target of rapamycin (mTOR) signaling pathway is involved in both genetic and acquired epilepsy syndromes. Excessive activation of mTOR signaling, as a consequence of loss-of-function of genes encoding for tuberous sclerosis complex (TSC) 1 and 2, is linked to the development of cortical malformations and epilepsy. This mTOR hyperactivation is associated with different epileptogenic conditions under the term of 'mTORopathies' such as tuberous sclerosis, focal cortical dysplasia, hemimegalencephaly and ganglioglioma. mTOR overactivation produces brain abnormalities that include dysplastic neurons, abnormal cortical organization and astrogliosis. mTOR inhibitors (e.g. rapamycin) have consistent protective effects in various genetic (e.g. TSC models and WAG/Rij rats) and acquired (e.g. kainate or pilocarpine post-status epilepticus) epilepsy animal models. Furthermore, clinical studies in patients with TSC and cortical dysplasia (CD) have confirmed the effectiveness of mTOR inhibitors also in epileptic patients. Therefore, mTOR is currently a very good candidate as a target for epilepsy and epileptogenesis. This review describes the relevance of the mTOR pathway to epileptogenesis and its potential as a therapeutic target in epilepsy treatment by presenting the most recent findings on mTOR inhibitors.

Type: Article
Title: mTOR pathway inhibition as a new therapeutic strategy in epilepsy and epileptogenesis.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.phrs.2016.03.039
Publisher version: http://dx.doi.org/10.1016/j.phrs.2016.03.039
Language: English
Keywords: Animal epilepsy models, Epilepsy, Epileptogenesis, Tuberous sclerosis complex, mTOR, mTOR inhibitors
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1478348
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