PMID- 34478688 OWN - NLM STAT- MEDLINE DCOM- 20220128 LR - 20220128 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 910 DP - 2021 Nov 5 TI - An insight into crosstalk among multiple signaling pathways contributing to epileptogenesis. PG - 174469 LID - S0014-2999(21)00623-3 [pii] LID - 10.1016/j.ejphar.2021.174469 [doi] AB - Despite the years of research, epilepsy remains uncontrolled in one-third of afflicted individuals and poses a health and economic burden on society. Currently available anti-epileptic drugs mainly target the excitatory-inhibitory imbalance despite targeting the underlying pathophysiology of the disease. Recent research focuses on understanding the pathophysiologic mechanisms that lead to seizure generation and on possible new treatment avenues for preventing epilepsy after a brain injury. Various signaling pathways, including the mechanistic target of rapamycin (mTOR) pathway, mitogen-activated protein kinase (MAP-ERK) pathway, JAK-STAT pathway, wnt/beta-catenin signaling, cAMP pathway, and jun kinase pathway, have been suggested to play an essential role in this regard. Recent work suggests that the mTOR pathway intervenes epileptogenesis and proposes that mTOR inhibitors may have antiepileptogenic properties for epilepsy. In the same way, several animal studies have indicated the involvement of the Wnt signaling pathway in neurogenesis and neuronal death induced by seizures in different phases (acute and chronic) of seizure development. Various studies have also documented the activation of JAK-STAT signaling in epilepsy and cAMP involvement in epileptogenesis through CREB (cAMP response element-binding protein). Although studies are there, the mechanism for how components of these pathways mediate epileptogenesis requires further investigation. This review summarises the current role of various signaling pathways involved in epileptogenesis and the crosstalk among them. Furthermore, we will also discuss the mechanical base for the interaction between these pathways and how these interactions could be a new emerging promising target for future epilepsy therapies. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Gautam, Vipasha AU - Gautam V AD - Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), 4th Floor, Research Block B, Chandigarh, 160012, India. FAU - Rawat, Kajal AU - Rawat K AD - Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), 4th Floor, Research Block B, Chandigarh, 160012, India. FAU - Sandhu, Arushi AU - Sandhu A AD - Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), 4th Floor, Research Block B, Chandigarh, 160012, India. FAU - Kumari, Puja AU - Kumari P AD - Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), 4th Floor, Research Block B, Chandigarh, 160012, India. FAU - Singh, Neha AU - Singh N AD - Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), 4th Floor, Research Block B, Chandigarh, 160012, India. FAU - Saha, Lekha AU - Saha L AD - Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), 4th Floor, Research Block B, Chandigarh, 160012, India. Electronic address: lekhasaha@rediffmail.com. LA - eng PT - Journal Article PT - Review DEP - 20210901 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Anticonvulsants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Anticonvulsants/*pharmacology/therapeutic use MH - Apoptosis/drug effects MH - Brain-Derived Neurotrophic Factor/blood/*metabolism MH - Cyclic AMP Response Element-Binding Protein/blood/*metabolism MH - Disease Models, Animal MH - Epilepsy/blood/drug therapy/*etiology/physiopathology MH - Glycogen Synthase Kinase 3 beta/metabolism MH - Humans MH - Neurons/drug effects/pathology/physiology MH - Signal Transduction/drug effects/physiology MH - TOR Serine-Threonine Kinases/metabolism OTO - NOTNLM OT - Epileptogenesis OT - JAK-STAT OT - MAP/ERK OT - PI3K/Akt OT - Wnt/beta-catenin OT - c-jun/JNK OT - cAMP OT - mTOR EDAT- 2021/09/04 06:00 MHDA- 2022/01/29 06:00 CRDT- 2021/09/03 20:11 PHST- 2021/06/21 00:00 [received] PHST- 2021/08/16 00:00 [revised] PHST- 2021/08/30 00:00 [accepted] PHST- 2021/09/04 06:00 [pubmed] PHST- 2022/01/29 06:00 [medline] PHST- 2021/09/03 20:11 [entrez] AID - S0014-2999(21)00623-3 [pii] AID - 10.1016/j.ejphar.2021.174469 [doi] PST - ppublish SO - Eur J Pharmacol. 2021 Nov 5;910:174469. doi: 10.1016/j.ejphar.2021.174469. Epub 2021 Sep 1.