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Author Altimiras, F.; Garcia, J.A.; Palacios-Garcia, I.; Hurley, M.J.; Deacon, R.; Gonzalez, B.; Cogram, P.
Title Altered Gut Microbiota in a Fragile X Syndrome Mouse Model Type
Year 2021 Publication Frontiers in Neuroscience Abbreviated Journal Front. Neurosci.
Volume 15 Issue Pages 653120
Keywords AKKERMANSIA-MUCINIPHILA; BRAIN; AUTISM; METABOLISM; ECOLOGY; HEALTH; BOWEL
Abstract The human gut microbiome is the ecosystem of microorganisms that live in the human digestive system. Several studies have related gut microbiome variants to metabolic, immune and nervous system disorders. Fragile X syndrome (FXS) is a neurodevelopmental disorder considered the most common cause of inherited intellectual disability and the leading monogenetic cause of autism. The role of the gut microbiome in FXS remains largely unexplored. Here, we report the results of a gut microbiome analysis using a FXS mouse model and 16S ribosomal RNA gene sequencing. We identified alterations in the fmr1 KO2 gut microbiome associated with different bacterial species, including those in the genera Akkermansia, Sutterella, Allobaculum, Bifidobacterium, Odoribacter, Turicibacter, Flexispira, Bacteroides, and Oscillospira. Several gut bacterial metabolic pathways were significantly altered in fmr1 KO2 mice, including menaquinone degradation, catechol degradation, vitamin B6 biosynthesis, fatty acid biosynthesis, and nucleotide metabolism. Several of these metabolic pathways, including catechol degradation, nucleotide metabolism and fatty acid biosynthesis, were previously reported to be altered in children and adults with autism. The present study reports a potential association of the gut microbiome with FXS, thereby opening new possibilities for exploring reliable treatments and non-invasive biomarkers.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1662-453X ISBN Medium
Area Expedition Conference
Notes WOS:000659516900001 Approved
Call Number UAI @ alexi.delcanto @ Serial 1415
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Author Deacon, R.M.J.; Hurley, M.J.; Rebolledo, C.M.; Snape, M.; Altimiras, F.J.; Farias, L.; Pino, M.; Biekofsky, R.; Glass, L.; Cogram, P.
Title Nrf2: a novel therapeutic target in fragile X syndrome is modulated by NNZ2566 Type
Year 2017 Publication Genes Brain And Behavior Abbreviated Journal Genes Brain Behav.
Volume 16 Issue 7 Pages 1-10
Keywords Autism spectrum disorder; behavior; E-cadherin; Fmr1 knockout mouse; fragile X syndrome; GST-alpha 1; NNZ2566; NQO1; Nrf2/ARE pathway; oxidative stress
Abstract Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders, fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and autism. Progress in basic neuroscience has led to identification of molecular targets for treatment in FXS; however, there is a gap in translation to targeted therapies in humans. This study introduces a novel therapeutic target for FXS, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor known to induce expression of over 100 cytoprotective genes. We also show that NNZ2566, a drug that has successfully completed a phase 2 clinical trial in FXS, is effective in modulating this target in FXS, partially reversing the FXS phenotype; NNZ2566 has a therapeutic role as Nrf2 activator. Effectively, treatment with NNZ2566 normalizes the translocation of Nrf2 to the nucleus, inducing expression of numerous oxidative stress-related genes including NQO1 (NAD(P) H dehydrogenase quinone 1), GST-alpha 1 (glutathione S-transferase alpha-1) and EH (epoxide hydrolase) and has a knockdown effect on E-cadherin. In summary, the Nrf2/ARE (antioxidant response element) pathway appears to be a novel promising therapeutic target for FXS and NNZ2566 appears to be acting as an activator of the Nrf2/ARE pathway and suggests a potential benefit across multiple symptoms that could be associated with the pathobiological processes underlying FXS.
Address [Deacon, R. M. J.; Altimiras, F. J.; Farias, L.; Pino, M.; Cogram, P.] Fraunhofer Res Fdn, Biomed Div, Ctr Syst Biotechnol, Santiago, Chile, Email: robertmj.deacon@gmail.com;
Corporate Author Thesis
Publisher Wiley Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1601-1848 ISBN Medium
Area Expedition Conference
Notes WOS:000410314200008 Approved
Call Number UAI @ eduardo.moreno @ Serial 861
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