6450d8f2de94e804009ac0405846078f pmc_31905931.pdf 58d832a4c355db60bca10fcedb2d2860b03c24ff pmc_31905931.pdf babbb02e526efa143caf98963f4453653323e04282c1f00dc883373a0233e981 pmc_31905931.pdf Title: Role of c-Jun N-Terminal Kinases (JNKs) in Epilepsy and Metabolic Cognitive Impairment Subject: Previous studies have reported that the regulatory function of the different c-Jun N-terminal kinases isoforms (JNK1, JNK2, and JNK3) play an essential role in neurological disorders, such as epilepsy and metabolic-cognitive alterations. Accordingly, JNKs have emerged as suitable therapeutic strategies. In fact, it has been demonstrated that some unspecific JNK inhibitors exert antidiabetic and neuroprotective effects, albeit they usually show high toxicity or lack therapeutic value. In this sense, natural specific JNK inhibitors, such as Licochalcone A, are promising candidates. Nonetheless, research on the understanding of the role of each of the JNKs remains mandatory in order to progress on the identification of new selective JNK isoform inhibitors. In the present review, a summary on the current gathered data on the role of JNKs in pathology is presented, as well as a discussion on their potential role in pathologies like epilepsy and metabolic-cognitive injury. Moreover, data on the effects of synthetic small molecule inhibitors that modulate JNK-dependent pathways in the brain and peripheral tissues is reviewed. Keywords: brain; epilepsy; metabolism; type 2 diabetes; c-Jun-N-terminal kinase; JNK inhibitor; cognitive impairment Author: Oriol Busquets, Miren Ettcheto, Amanda Cano, Patricia R. Manzine, Elena Sánchez-Lopez, Triana Espinosa-Jiménez, Ester Verdaguer, Rubén Dario Castro-Torres, Carlos Beas-Zarate, Francesc X. Sureda, Jordi Olloquequi, Carme Auladell, Jaume Folch and Antoni Camins Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Mon Dec 30 11:39:08 2019 CET ModDate: Mon Dec 30 11:39:08 2019 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1610009 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- DVTERF+URWPalladioL-Ital Type 1 Custom yes yes no 86 0 GCIYKS+URWPalladioL-Bold Type 1 Custom yes yes no 87 0 GIFXFT+VnURWPalladioL-Bold Type 1 Custom yes yes no 88 0 QTLELQ+Pxbsy Type 1 Builtin yes yes no 89 0 KWYEQD+URWPalladioL-Roma Type 1 Custom yes yes no 90 0 WRPPZE+VnURWPalladioL Type 1 Custom yes yes no 91 0 MHAHCD+Rpxr Type 1 Builtin yes yes no 92 0 PBPPUU+Pxsy Type 1 Builtin yes yes no 93 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C 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きどぴはでづのぜ〴ぜ〰ぁっぴどぶちぴづつぜ〴ぜ〰ぐひはぴづどのぜ〴ぜ〰かどのちびづびぜ〴ぜ〰ぜ〵ぜ〰きぁぐかびぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぃ〭おさぎぜ〴ぜ〰ぎ〭ごづひねどのちぬぜ〴ぜ〰かどのちびづびぜ〴ぜ〰ぜ〵ぜ〰おぎかびぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰げはぬづぜ〴ぜ〰はてぜ〴ぜ〰おぎかびぜ〴ぜ〰どのぜ〴ぜ〰こふぢっづぬぬふぬちひぜ〴ぜ〰ぃはねばちひぴねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸱ Children: Item: Title: げはぬづぜ〴ぜ〰はてぜ〴ぜ〰おぎかびぜ〴ぜ〰どのぜ〴ぜ〰こふぢっづぬぬふぬちひぜ〴ぜ〰ぃはねばちひぴねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸱ Children: Item: Title: おぎかぜ〴ぜ〰ぁっぴどぶちぴどはのぜ〴ぜ〰ぁぬぴづひびぜ〴ぜ〰きどぴはっとはのつひどちぬぜ〴ぜ〰ぁっぴどぶどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸲ Item: Title: ぅのつはばぬちびねどっぜ〴ぜ〰げづぴどっふぬふねぜ〴ぜ〰こぴひづびびぜ〴ぜ〰ぜ〵ぜ〰ぅげこぜ〵ㅜ〰ぜ〴ぜ〰ぁっぴどぶちぴづびぜ〴ぜ〰おぎかぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰おぎかびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰あひちどのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: おぎかびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰あひちどのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: げはぬづぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰おぎかびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰いづぶづぬはばねづのぴぜ〴ぜ〰はてぜ〴ぜ〰いどびづちびづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮ㄩ‾㸊⡜㌷㙜㌷㝜〰ごづねばはひちぬぜ〴ぜ〰がはぢづぜ〴ぜ〰ぅばどぬづばびべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ごとづぜ〴ぜ〰きづぴちぢはぬどっ〭ぃはでのどぴどぶづぜ〴ぜ〰こべのつひはねづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸲⸱ Children: Item: Title: ごづねばはひちぬぜ〴ぜ〰がはぢづぜ〴ぜ〰ぅばどぬづばびべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ごとづぜ〴ぜ〰きづぴちぢはぬどっ〭ぃはでのどぴどぶづぜ〴ぜ〰こべのつひはねづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸲⸱ Item: Title: ごとづぜ〴ぜ〰きづぴちぢはぬどっ〭ぃはでのどぴどぶづぜ〴ぜ〰こべのつひはねづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸲⸱ Children: Item: Title: ごとづぜ〴ぜ〰きづぴちぢはぬどびねぜ〴ぜ〰はてぜ〴ぜ〰ぉのびふぬどのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸲⸲ Item: Title: ごとづぜ〴ぜ〰きづぴちぢはぬどびねぜ〴ぜ〰はてぜ〴ぜ〰ぉのびふぬどのぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰あひちどのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸲⸳ Item: Title: げはぬづぜ〴ぜ〰はてぜ〴ぜ〰おぎかびぜ〴ぜ〰どのぜ〴ぜ〰きづぴちぢはぬどっ〭げづぬちぴづつぜ〴ぜ〰いづねづのぴどちびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: おぎかびぜ〴ぜ〰ちびぜ〴ぜ〰ぐはぴづのぴどちぬぜ〴ぜ〰ごとづひちばづふぴどっぜ〴ぜ〰ごちひでづぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸶ Item: Title: ぃはのっぬふつどのでぜ〴ぜ〰げづねちひにびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸶ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: VSHNAE+Rpcxr FontSubset: true FirstChar: 169 LastChar: 169 FontDescriptor: FontName: VSHNAE+Rpcxr Flags: Symbolic FontBBox: -212, -286, 1344, 973 FontFile: true Font: BaseFont: DVTERF+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 122 FontDescriptor: FontName: DVTERF+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, 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