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New insight into transglutaminase 2 and link to neurodegenerative diseases

Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer’s, Parkinson’s, Huntington’s, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multif...

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Autores principales: Min, Boram, Chung, Kwang Chul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796628/
https://www.ncbi.nlm.nih.gov/pubmed/29187283
http://dx.doi.org/10.5483/BMBRep.2018.51.1.227
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author Min, Boram
Chung, Kwang Chul
author_facet Min, Boram
Chung, Kwang Chul
author_sort Min, Boram
collection PubMed
description Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer’s, Parkinson’s, Huntington’s, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional enzyme, displaying four types of activity, such as transamidation, GTPase, protein disulfide isomerase, and protein kinase activities. Many studies demonstrated that the calcium-dependent transamidation activity of TG2 affects the formation of insoluble and toxic amyloid aggregates that mainly consisted of NDD-related proteins. So far, many important and NDD-related substrates of TG2 have been identified, including amlyoid-β, tau, α-synuclein, mutant huntingtin, and ALS-linked trans-activation response (TAR) DNA-binding protein 43. Recently, the formation of toxic inclusions mediated by several TG2 substrates were efficiently inhibited by TG2 inhibitors. Therefore, the development of highly specific TG2 inhibitors would be an important tool in alleviating the progression of TG2-related brain disorders. In this review, the authors discuss recent advances in TG2 biochemistry, several mechanisms of molecular regulation and pleotropic signaling functions, and the presumed role of TG2 in the progression of many NDDs.
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spelling pubmed-57966282018-02-21 New insight into transglutaminase 2 and link to neurodegenerative diseases Min, Boram Chung, Kwang Chul BMB Rep Invited Mini Review Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer’s, Parkinson’s, Huntington’s, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional enzyme, displaying four types of activity, such as transamidation, GTPase, protein disulfide isomerase, and protein kinase activities. Many studies demonstrated that the calcium-dependent transamidation activity of TG2 affects the formation of insoluble and toxic amyloid aggregates that mainly consisted of NDD-related proteins. So far, many important and NDD-related substrates of TG2 have been identified, including amlyoid-β, tau, α-synuclein, mutant huntingtin, and ALS-linked trans-activation response (TAR) DNA-binding protein 43. Recently, the formation of toxic inclusions mediated by several TG2 substrates were efficiently inhibited by TG2 inhibitors. Therefore, the development of highly specific TG2 inhibitors would be an important tool in alleviating the progression of TG2-related brain disorders. In this review, the authors discuss recent advances in TG2 biochemistry, several mechanisms of molecular regulation and pleotropic signaling functions, and the presumed role of TG2 in the progression of many NDDs. Korean Society for Biochemistry and Molecular Biology 2018-01 2018-01-31 /pmc/articles/PMC5796628/ /pubmed/29187283 http://dx.doi.org/10.5483/BMBRep.2018.51.1.227 Text en Copyright © 2018 by the The Korean Society for Biochemistry and Molecular Biology http://creativecommons.org/licenses/by-nc/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Invited Mini Review
Min, Boram
Chung, Kwang Chul
New insight into transglutaminase 2 and link to neurodegenerative diseases
title New insight into transglutaminase 2 and link to neurodegenerative diseases
title_full New insight into transglutaminase 2 and link to neurodegenerative diseases
title_fullStr New insight into transglutaminase 2 and link to neurodegenerative diseases
title_full_unstemmed New insight into transglutaminase 2 and link to neurodegenerative diseases
title_short New insight into transglutaminase 2 and link to neurodegenerative diseases
title_sort new insight into transglutaminase 2 and link to neurodegenerative diseases
topic Invited Mini Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796628/
https://www.ncbi.nlm.nih.gov/pubmed/29187283
http://dx.doi.org/10.5483/BMBRep.2018.51.1.227
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