mTOR pathway inhibition as a new therapeutic strategy in epilepsy and epileptogenesis
[Display omitted] 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 fo...
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| Published in | Pharmacological research Vol. 107; pp. 333 - 343 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier Ltd
01.05.2016
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| Subjects | |
| Online Access | Get full text |
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| Abstract | [Display omitted]
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. |
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| AbstractList | 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. [Display omitted] 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. |
| Author | Russo, Emilio Citraro, Rita De Sarro, Giovambattista Leo, Antonio Constanti, Andrew |
| Author_xml | – sequence: 1 givenname: Rita surname: Citraro fullname: Citraro, Rita organization: Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Italy – sequence: 2 givenname: Antonio surname: Leo fullname: Leo, Antonio organization: Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Italy – sequence: 3 givenname: Andrew surname: Constanti fullname: Constanti, Andrew organization: Department of Pharmacology, UCL School of Pharmacy, 29/39 Brunswick Square, London, United Kingdom, UK – sequence: 4 givenname: Emilio surname: Russo fullname: Russo, Emilio organization: Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Italy – sequence: 5 givenname: Giovambattista surname: De Sarro fullname: De Sarro, Giovambattista email: desarro@unicz.it organization: Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Italy |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27049136$$D View this record in MEDLINE/PubMed |
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Several preclinical and some clinical studies have revealed that the mammalian target of rapamycin (mTOR) signaling pathway is involved in... Several preclinical and some clinical studies have revealed that the mammalian target of rapamycin (mTOR) signaling pathway is involved in both genetic and... |
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| SubjectTerms | Animal epilepsy models Animals Epilepsy Epilepsy - drug therapy Epilepsy - metabolism Epileptogenesis Humans mTOR mTOR inhibitors TOR Serine-Threonine Kinases - antagonists & inhibitors TOR Serine-Threonine Kinases - metabolism Tuberous sclerosis complex |
| Title | mTOR pathway inhibition as a new therapeutic strategy in epilepsy and epileptogenesis |
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