9dacb53b512ec1236b7351eda9074f38 pmc_32429516.pdf bf7ef6f2a42c17a3d9952e158b03779e9cfe126b pmc_32429516.pdf 63ff3f6f1e590f911592932a34045e3b84462ed53bbe70df0a125eae93787447 pmc_32429516.pdf Title: Neuroprotective Fragment C of Tetanus Toxin Modulates IL-6 in an ALS Mouse Model Subject: Neuroinflammation plays a significant role in amyotrophic lateral sclerosis (ALS) pathology, leading to the development of therapies targeting inflammation in recent years. Our group has studied the tetanus toxin C-terminal fragment (TTC) as a therapeutic molecule, showing neuroprotective properties in the SOD1G93A mouse model. However, it is unknown whether TTC could have some effect on inflammation. The objective of this study was to assess the effect of TTC on the regulation of inflammatory mediators to elucidate its potential role in modulating inflammation occurring in ALS. After TTC treatment in SOD1G93A mice, levels of eotaxin-1, interleukin (IL)-2, IL-6 and macrophage inflammatory protein (MIP)-1 alpha () and galectin-1 were analyzed by immunoassays in plasma samples, whilst protein expression of caspase-1, IL-1, IL-6 and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) was measured in the spinal cord, extensor digitorum longus (EDL) muscle and soleus (SOL) muscle. The results showed reduced levels of IL-6 in spinal cord, EDL and SOL in treated SOD1G93A mice. In addition, TTC showed a different role in the modulation of NLRP3 and caspase-1 depending on the tissue analyzed. In conclusion, our results suggest that TTC could have a potential anti-inflammatory effect by reducing IL-6 levels in tissues drastically affected by the disease. However, further research is needed to study more in depth the anti-inflammatory effect of TTC in ALS. Keywords: TTC; amyotrophic lateral sclerosis; inflammation; SOD1G93A mouse model Author: Laura Moreno-Martinez, Miriam de la Torre, María J. Muñoz, Pilar Zaragoza, José Aguilera, Ana C. Calvo and Rosario Osta Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Sun May 17 09:23:26 2020 CEST ModDate: Sun May 17 09:23:26 2020 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1284865 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- LSPTSG+URWPalladioL-Ital Type 1 Custom yes yes no 79 0 ZNACEN+URWPalladioL-Bold Type 1 Custom yes yes no 80 0 YSPQJI+VnURWPalladioL-Bold Type 1 Custom yes yes no 81 0 LFMWWE+URWPalladioL-Roma Type 1 Custom yes yes no 82 0 LWJOET+VnURWPalladioL Type 1 Custom yes yes no 83 0 TYBPRH+Rpxr Type 1 Builtin yes yes no 84 0 VVSYYB+EURM10 Type 1 Builtin yes yes no 85 0 DVMWWR+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 91 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 108 0 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(Rel. 1.22.1, 2019-04-17) Date: 2020-11-18 06:38:31 CET RepresentationInformation: pmc_32429516.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-07-06 03:43:11 CEST Size: 1284865 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰ごごぃぜ〴ぜ〰いどつぜ〴ぜ〰ぎはぴぜ〴ぜ〰げづつふっづぜ〴ぜ〰ぁのべぜ〴ぜ〰ぃべぴはにどのづぜ〴ぜ〰どのぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰てひはねぜ〴ぜ〰こくい〱ぇ〹〳ぁぜ〴ぜ〰きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ごごぃぜ〴ぜ〰いどててづひづのぴぬべぜ〴ぜ〰きはつふぬちぴづびぜ〴ぜ〰ぴとづぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰ぎがげぐ〳〬ぜ〴ぜ〰ぃちびばちびづ〭〱ぜ〴ぜ〰ちのつぜ〴ぜ〰ぉが〭〶ぜ〴ぜ〰どのぜ〴ぜ〰こばどのちぬぜ〴ぜ〰ぃはひつぜ〴ぜ〰ちのつぜ〴ぜ〰ごぷはぜ〴ぜ〰ごべばづびぜ〴ぜ〰はてぜ〴ぜ〰こにづぬづぴちぬぜ〴ぜ〰きふびっぬづぜ〴ぜ〰うどぢづひびぜ〴ぜ〰てひはねぜ〴ぜ〰こくい〱ぇ〹〳ぁぜ〴ぜ〰きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: ごごぃぜ〴ぜ〰いどつぜ〴ぜ〰ぎはぴぜ〴ぜ〰げづつふっづぜ〴ぜ〰ぁのべぜ〴ぜ〰ぃべぴはにどのづぜ〴ぜ〰どのぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰てひはねぜ〴ぜ〰こくい〱ぇ〹〳ぁぜ〴ぜ〰きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ごごぃぜ〴ぜ〰いどててづひづのぴぬべぜ〴ぜ〰きはつふぬちぴづびぜ〴ぜ〰ぴとづぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰ぎがげぐ〳〬ぜ〴ぜ〰ぃちびばちびづ〭〱ぜ〴ぜ〰ちのつぜ〴ぜ〰ぉが〭〶ぜ〴ぜ〰どのぜ〴ぜ〰こばどのちぬぜ〴ぜ〰ぃはひつぜ〴ぜ〰ちのつぜ〴ぜ〰ごぷはぜ〴ぜ〰ごべばづびぜ〴ぜ〰はてぜ〴ぜ〰こにづぬづぴちぬぜ〴ぜ〰きふびっぬづぜ〴ぜ〰うどぢづひびぜ〴ぜ〰てひはねぜ〴ぜ〰こくい〱ぇ〹〳ぁぜ〴ぜ〰きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ごごぃぜ〴ぜ〰いどててづひづのぴぬべぜ〴ぜ〰きはつふぬちぴづびぜ〴ぜ〰ぴとづぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰ぎがげぐ〳〬ぜ〴ぜ〰ぃちびばちびづ〭〱ぜ〴ぜ〰ちのつぜ〴ぜ〰ぉが〭〶ぜ〴ぜ〰どのぜ〴ぜ〰こばどのちぬぜ〴ぜ〰ぃはひつぜ〴ぜ〰ちのつぜ〴ぜ〰ごぷはぜ〴ぜ〰ごべばづびぜ〴ぜ〰はてぜ〴ぜ〰こにづぬづぴちぬぜ〴ぜ〰きふびっぬづぜ〴ぜ〰うどぢづひびぜ〴ぜ〰てひはねぜ〴ぜ〰こくい〱ぇ〹〳ぁぜ〴ぜ〰きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: きちぴづひどちぬびぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぁのどねちぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㈩‾㸊⡜㌷㙜㌷㝜〰ごひづちぴねづのぴぜ〴ぜ〰ぷどぴとぜ〴ぜ〰げづっはねぢどのちのぴぜ〴ぜ〰ごごぃぜ〴ぜ〰ぐひはぴづどのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㌩‾㸊⡜㌷㙜㌷㝜〰こちねばぬづぜ〴ぜ〰ぃはぬぬづっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㐩‾㸊⡜㌷㙜㌷㝜〰ぅがぉこぁぜ〴ぜ〰ちのつぜ〴ぜ〰きふぬぴどばぬづへぜ〴ぜ〰ぉねねふのはちびびちべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㔩‾㸊⡜㌷㙜㌷㝜〰しづびぴづひのぜ〴ぜ〰あぬはぴぴどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Children: Item: Title: ぁのどねちぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㈩‾㸊⡜㌷㙜㌷㝜〰ごひづちぴねづのぴぜ〴ぜ〰ぷどぴとぜ〴ぜ〰げづっはねぢどのちのぴぜ〴ぜ〰ごごぃぜ〴ぜ〰ぐひはぴづどのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㌩‾㸊⡜㌷㙜㌷㝜〰こちねばぬづぜ〴ぜ〰ぃはぬぬづっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㐩‾㸊⡜㌷㙜㌷㝜〰ぅがぉこぁぜ〴ぜ〰ちのつぜ〴ぜ〰きふぬぴどばぬづへぜ〴ぜ〰ぉねねふのはちびびちべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㔩‾㸊⡜㌷㙜㌷㝜〰しづびぴづひのぜ〴ぜ〰あぬはぴぴどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: ごひづちぴねづのぴぜ〴ぜ〰ぷどぴとぜ〴ぜ〰げづっはねぢどのちのぴぜ〴ぜ〰ごごぃぜ〴ぜ〰ぐひはぴづどのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㌩‾㸊⡜㌷㙜㌷㝜〰こちねばぬづぜ〴ぜ〰ぃはぬぬづっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㐩‾㸊⡜㌷㙜㌷㝜〰ぅがぉこぁぜ〴ぜ〰ちのつぜ〴ぜ〰きふぬぴどばぬづへぜ〴ぜ〰ぉねねふのはちびびちべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㔩‾㸊⡜㌷㙜㌷㝜〰しづびぴづひのぜ〴ぜ〰あぬはぴぴどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: こちねばぬづぜ〴ぜ〰ぃはぬぬづっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㐩‾㸊⡜㌷㙜㌷㝜〰ぅがぉこぁぜ〴ぜ〰ちのつぜ〴ぜ〰きふぬぴどばぬづへぜ〴ぜ〰ぉねねふのはちびびちべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㔩‾㸊⡜㌷㙜㌷㝜〰しづびぴづひのぜ〴ぜ〰あぬはぴぴどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: ぅがぉこぁぜ〴ぜ〰ちのつぜ〴ぜ〰きふぬぴどばぬづへぜ〴ぜ〰ぉねねふのはちびびちべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㔩‾㸊⡜㌷㙜㌷㝜〰しづびぴづひのぜ〴ぜ〰あぬはぴぴどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: しづびぴづひのぜ〴ぜ〰あぬはぴぴどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㔮㘩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: 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