Abstract
The role of phosphatidylinositol 3-kinase linked mammalian target of rapamycin (mTOR) pathway hyperactivation is well established in cancer pathogenesis. Several molecules inhibiting mTOR pathway, leading to inhibition of protein synthesis responsible for angiogenesis of tumor cells have emerged out to be potential anticancers. Similar hyperactivation of mTOR pathway has also reported in epilepsy during latent phase, following precipitating injury causing reorganization of neuronal networks and ultimately leading to induction of seizures. The mTOR inhibitors have also found to attenuate pathological changes in the brain associated with epilepsy, primarily suppression of mossy fiber sprouting. At the same time, a few antiepileptic molecules which have been studied against cancer showed anticancer activity, apart from their principal mechanism of action. These studies suggest mTOR signaling pathway to be a common pathogenic link between cancer and epilepsy. It has been found that, anticancer molecules acting on different molecular targets, that ultimately down regulate the expression of mTOR, can also be used in case of epilepsy to reduce its hyperactivation. There are several unexplored anticancer molecules that act by inhibiting mTOR directly or indirectly available which can be explored as antiepileptic in future. Majority of the molecules which are tested as anticancer do not reach the final phases of clinical trials due to less potency and efficacy, and ultimately a few of them reach the market. Since a lot of experimental/safety studies have already been conducted on such molecules, hence it is worthwhile to test these molecules for other disorders that share common pathogenic pathway like epilepsy, provided their pitfalls have been addressed, as proposed in the present review.
Keywords: Epilepsy, hippocampus, mossy fiber sprouting, rapamycin, traumatic brain injury, tuberous sclerosis complex.
CNS & Neurological Disorders - Drug Targets
Title:Anticancer Mammalian Target of Rapamycin (mTOR) Signaling Pathway Inhibitors: Current Status, Challenges and Future Prospects in Management of Epilepsy
Volume: 15 Issue: 8
Author(s): Arindam Ghosh Mazumder, Yogendra Shantaram Padwad and Damanpreet Singh
Affiliation:
Keywords: Epilepsy, hippocampus, mossy fiber sprouting, rapamycin, traumatic brain injury, tuberous sclerosis complex.
Abstract: The role of phosphatidylinositol 3-kinase linked mammalian target of rapamycin (mTOR) pathway hyperactivation is well established in cancer pathogenesis. Several molecules inhibiting mTOR pathway, leading to inhibition of protein synthesis responsible for angiogenesis of tumor cells have emerged out to be potential anticancers. Similar hyperactivation of mTOR pathway has also reported in epilepsy during latent phase, following precipitating injury causing reorganization of neuronal networks and ultimately leading to induction of seizures. The mTOR inhibitors have also found to attenuate pathological changes in the brain associated with epilepsy, primarily suppression of mossy fiber sprouting. At the same time, a few antiepileptic molecules which have been studied against cancer showed anticancer activity, apart from their principal mechanism of action. These studies suggest mTOR signaling pathway to be a common pathogenic link between cancer and epilepsy. It has been found that, anticancer molecules acting on different molecular targets, that ultimately down regulate the expression of mTOR, can also be used in case of epilepsy to reduce its hyperactivation. There are several unexplored anticancer molecules that act by inhibiting mTOR directly or indirectly available which can be explored as antiepileptic in future. Majority of the molecules which are tested as anticancer do not reach the final phases of clinical trials due to less potency and efficacy, and ultimately a few of them reach the market. Since a lot of experimental/safety studies have already been conducted on such molecules, hence it is worthwhile to test these molecules for other disorders that share common pathogenic pathway like epilepsy, provided their pitfalls have been addressed, as proposed in the present review.
Export Options
About this article
Cite this article as:
Mazumder Ghosh Arindam, Padwad Shantaram Yogendra and Singh Damanpreet, Anticancer Mammalian Target of Rapamycin (mTOR) Signaling Pathway Inhibitors: Current Status, Challenges and Future Prospects in Management of Epilepsy, CNS & Neurological Disorders - Drug Targets 2016; 15 (8) . https://dx.doi.org/10.2174/1871527315666160615022203
DOI https://dx.doi.org/10.2174/1871527315666160615022203 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Heart and Brain Axis Targets in CNS Neurological Disorders
Recently there has been a surge of interest in delving deeper into the complex interplay between the heart and brain. This fascination stems from a growing recognition of the profound influence each organ holds over the other, particularly in the realm of central nervous system (CNS) neurological disorders. The purpose ...read more
Lifestyle Interventions to Prevent and Treat Cognitive Impairment and Dementia
More than 55 million people live with dementia worldwide. By 2050, the population affected by dementia will exceed 139 million individuals. Mild cognitive impairment (MCI) is a pre-dementia stage, also known as prodromal dementia, affecting older adults. MCI emerges years before the manifestation of dementia but can be avoidable and ...read more
Novel Treatments in Subarachnoid Hemorrhage
The current landscape of therapeutic strategies for subarachnoid hemorrhage (SAH), a significant adverse neurological event commonly resulting from the rupture of intracranial aneurysms, is rapidly evolving. Through an in-depth exploration of the natural history of SAH, historical treatment approaches, and emerging management modalities, the present work aims to provide a ...read more
Pathogenic Proteins in Neurodegenerative Diseases: From Mechanisms to Treatment Modalities
The primary objective of this thematic issue is to elucidate the molecular mechanisms by which pathogenic proteins contribute to neurodegenerative diseases and to highlight current and emerging therapeutic strategies aimed at mitigating their effects. By bringing together cutting-edge research and reviews, this issue aims to: 1.Enhance Understanding: Provide a comprehensive ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Treating Asthma as a Neuroelectrical Disorder
Inflammation & Allergy - Drug Targets (Discontinued) Osteopontin as a Potential Therapeutic Target for Ischemic Stroke
Current Drug Delivery Investigation of the Metabolism of Rufinamide and Its Interaction with Valproate
Drug Metabolism Letters Implications of Herbal Components in the Treatment of Neurological Disorders
Current Nutrition & Food Science Editorial [ Hot topic:Psychogenomics and Psychiatric Practice, a New Paradigm (Guest Editor: Tih-Shih Lee)]
Current Psychiatry Reviews The Evolution of Schizophrenia: A Model for Selection by Infection, with a Focus on NAD
Current Pharmaceutical Design Anti-seizure Medications: Challenges and Opportunities
CNS & Neurological Disorders - Drug Targets Natural Antioxidants of the Underutilized and Neglected Plant Species of Asia and South America
Letters in Drug Design & Discovery Subject Index to Volume 5
Current Drug Targets BDZs, Designer BDZs and Z-drugs: Pharmacology and Misuse Insights
Current Pharmaceutical Design Filtering Disturbances in Schizophrenic Patients. Gating of Auditory Evoked Potentials and Prepulse Inhibition of the Acoustic Startle Response Compared. Emphasis on the Role of Dopamine
Current Neuropharmacology Therapeutic Potential of Natural Products from Terrestrial Plants as TNF-α Antagonist
Current Topics in Medicinal Chemistry Green Chemistry Approach for the Synthesis of Isoxazole Derivatives and Evaluation of their Anti-epileptic Activity
Current Drug Discovery Technologies Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review
Drug Delivery Letters Voltage-Gated Sodium Channels: Mutations, Channelopathies and Targets
Current Medicinal Chemistry A Review on Synthesis of Benzothiazole Derivatives
Current Organocatalysis A Computational Prediction of Conserved MicroRNA Targets of Ion Channels in Vertebrates
Current Bioinformatics HtrA Serine Proteases as Potential Therapeutic Targets in Cancer
Current Cancer Drug Targets Targeting Glycogen Synthase Kinase-3 in the CNS: Implications for the Development of New Treatments for Mood Disorders
Current Drug Targets Kynurenic Acid and Neuroprotective Activity of the Ketogenic Diet in the Eye
Current Medicinal Chemistry