ArticleAnnals of neurology2018
Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy.
Article in Annals of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 75 citations in OpenAlex.
- Epilepsy as a Disorder of Neuroimmune Metabolism: The Kynurenine Pathway as a Link Between Cognitive and Psychiatric Dysfunction.Biomolecules · 2026Review
- Cell-Intrinsic Regulation of Epilepsy-Associated Pathology by mTORC1 and mTORC2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Molecular mechanisms of neurosteroids in temporal lobe epilepsy: current insights and therapeutic perspectives.Molecular biology reports · 2025Review
- Sex-specific proteomic analysis of epileptic brain tissues from Pten knockout mice and human refractory epilepsy.Experimental neurology · 2025Article
- Mechanistic insights into the interaction between epilepsy and sleep.Nature reviews. Neurology · 2025Review
- Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex.Acta neuropathologica · 2024Article
- mTORC2: The "Ace in the Hole" for a Broader Control of Epileptic Seizures?Neuroscience bulletin · 2024Article
- mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.Nature reviews. Neuroscience · 2024Review
- Hyperactivity of mTORC1- and mTORC2-dependent signaling mediates epilepsy downstream of somatic PTEN loss.eLife · 2024Article
- Hyperactivity of mTORC1 and mTORC2-dependent signaling mediate epilepsy downstream of somatic PTEN loss.bioRxiv : the preprint server for biology · 2024Article
- Targeted suppression of mTORC2 reduces seizures across models of epilepsy.Nature communications · 2023Article
- Seizure reduction in TSC2-mutant mouse model by an mTOR catalytic inhibitor.Annals of clinical and translational neurology · 2023Article
- Assessment of tau phosphorylation and β-amyloid pathology in human drug-resistant epilepsy.Epilepsia open · 2023Article
- Efficacy and mechanisms of Dingxian pill combined with valproic acid on pentylenetetrazol-induced chronic epilepsy in rats.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2023Article
- Advances and Challenges of Cannabidiol as an Anti-Seizure Strategy: Preclinical Evidence.International journal of molecular sciences · 2022Review
- Gene expression profile suggests different mechanisms underlying sporadic and familial mesial temporal lobe epilepsy.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Article
- Impact of Raptor and Rictor Deletion on Hippocampal Pathology Following Status Epilepticus.Journal of molecular neuroscience : MN · 2022Article
- Can rodent models elucidate the pathomechanisms of genetic epilepsy?British journal of pharmacology · 2022Review
- The role of mTORC1 activation in seizure-induced exacerbation of Alzheimer's disease.Brain : a journal of neurology · 2022Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveTemporal lobe epilepsy (TLE) is a chronic epilepsy syndrome defined by seizures and progressive neurological disabilities, including cognitive impairments, anxiety, and depression. Here, human TLE specimens were investigated focusing on the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and complex 2 (mTORC2) activities in the brain, given that both pathways may represent unique targets for treatment.
methodsSurgically resected hippocampal and temporal lobe samples from therapy-resistant TLE patients were analyzed by western blotting to quantify the expression of established mTORC1 and mTORC2 activity markers and upstream or downstream signaling pathways involving the two complexes. Histological and immunohistochemical techniques were used to assess hippocampal and neocortical structural abnormalities and cell-specific expression of individual biomarkers. Samples from patients with focal cortical dysplasia (FCD) type II served as positive controls.
resultsWe found significantly increased expression of phospho-mTOR (Ser2448), phospho-S6 (Ser235/236), phospho-S6 (Ser240/244), and phospho-Akt (Ser473) in TLE samples compared to controls, consistent with activation of both mTORC1 and mTORC2. Our work identified the phosphoinositide 3-kinase and Ras/extracellular signal-regulated kinase signaling pathways as potential mTORC1 and mTORC2 upstream activators. In addition, we found that overactive mTORC2 signaling was accompanied by induction of two protein kinase B-dependent prosurvival pathways, as evidenced by increased inhibitory phosphorylation of forkhead box class O3a (Ser253) and glycogen synthase kinase 3 beta (Ser9).
interpretationOur data demonstrate that mTOR signaling is significantly dysregulated in human TLE, offering new targets for pharmacological interventions. Specifically, clinically available drugs that suppress mTORC1 without compromising mTOR2 signaling, such as rapamycin and its analogs, may represent a new group of antiepileptogenic agents in TLE patients. Ann Neurol 2018;83:311-327.
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