Tuberous sclerosis‐associated epilepsy and intellectual disability: what role does the mammalian target of rapamycin pathway play?

Curatolo, Paolo

doi:10.1111/dmcn.14371

Cited by 2 publications

(2 citation statements)

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“…and new onset refractory SE (NORSE). MTOR inhibitors can also be used as an adjuvant therapy to reduce the inflammatory response of encephalitis in the clinic (Crino, 2019). In addition, rapamycin may inhibit the recurrent excitatory circuit in the dentate gyrus by inactivating the mTOR pathway and impeding mossy fiber germination after SE.…”

Section: Rapamycinmentioning

confidence: 99%

“…Mutations in active regulatory genes (TSC1, TSC2, AKT3, and DEPDC5) has been shown to cause activation of the mTOR signaling cascade, resulting in a series of pathological events associated with increased excitability and decreased seizure threshold, including celluar enlargement and morphological changes, dendritic morphology changes, dendritic spine density and structure changes, axonal regeneration, and cortical layering disorder due to altered neuronal movement (Crino, 2015). The mTOR cascade activation may be an important cause of TSC‐related epilepsy, a form of epilepsy caused by malformations of cortical development (MCDs) (Curatolo, 2020). In TSC1‐deleted mice, epilepsy occurs within a short time window (8‐12d) of TS and is accompanied by strong activation of the mTORC1 pathway, showing a dose‐dependent response to the mTORC1 inhibitor rapamycin.…”

Section: The Role Of the Mtor Signaling Pathway In Epilepsymentioning

confidence: 99%

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Advances in the mTOR signaling pathway and its inhibitor rapamycin in epilepsy

et al. 2023

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Introduction: Epilepsy is one of the most common and serious brain syndromes and has adverse consequences on a patient's neurobiological, cognitive, psychological, and social wellbeing, thereby threatening their quality of life. Some patients with epilepsy experience poor treatment effects due to the unclear pathophysiological mechanisms of the syndrome. Dysregulation of the mammalian target of the rapamycin (mTOR) pathway is thought to play an important role in the onset and progression of some epilepsies.Methods: This review summarizes the role of the mTOR signaling pathway in the pathogenesis of epilepsy and the prospects for the use of mTOR inhibitors. Results:The mTOR pathway functions as a vital mediator in epilepsy development through diverse mechanisms, indicating that the it has great potential as an effective target for epilepsy therapy. The excessive activation of mTOR signaling pathway leads to structural changes in neurons, inhibits autophagy, exacerbates neuron damage, affects mossy fiber sprouting, enhances neuronal excitability, increases neuroinflammation, and is closely associated with tau upregulation in epilepsy. A growing number of studies have demonstrated that mTOR inhibitors exhibit significant antiepileptic effects in both clinical applications and animal models. Specifically, rapamycin, a specific inhibitor of TOR, reduces the intensity and frequency of seizures. Clinical studies in patients with tuberous sclerosis complex have shown that rapamycin has the function of reducing seizures and improving this disease. Everolimus, a chemically modified derivative of rapamycin, has been approved as an added treatment to other antiepileptic medicines. Further explorations are needed to evaluate the therapeutic efficacy andThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Rapamycinmentioning

confidence: 99%

Section: The Role Of the Mtor Signaling Pathway In Epilepsymentioning

confidence: 99%