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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.1
- 수록면
- 5 - 13 (9page)
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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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참고문헌 (77)
참고문헌 신청
Sarkar NK / 1957 / An enzymically catalyzed incorporation of amines into proteins / Biochim Biophys Acta 25:451~452
Grenard P / 2001 / Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the gene encoding transglutaminase X and a novel gene family member, transglutaminase Z / J Biol Chem 276:33066~33078
Mehta K / 2005 / Mammalian transglutaminases: a family portrait / Prog Exp Tumor Res 38:1~18
Park D / 2010 / Transglutaminase 2: a multi-functional protein in multiple subcellular compartments / Amino Acids 39:619~631
Achyuthan KE / 1987 / Identification of a guanosine triphosphate-binding site on guinea pig liver transglutaminase. Role of GTP and calcium ions in modulating activity / J Biol Chem 262:1901~1906
Grenard P / 2001 / Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the gene encoding transglutaminase X and a novel gene family member, transglutaminase Z / J Biol Chem 276:33066~33078
Mehta K / 2005 / Mammalian transglutaminases: a family portrait / Prog Exp Tumor Res 38:1~18
Park D / 2010 / Transglutaminase 2: a multi-functional protein in multiple subcellular compartments / Amino Acids 39:619~631
Achyuthan KE / 1987 / Identification of a guanosine triphosphate-binding site on guinea pig liver transglutaminase. Role of GTP and calcium ions in modulating activity / J Biol Chem 262:1901~1906
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