New insight into transglutaminase 2 and link to neurodegenerative diseases

Boram Min, Kwang Chul Chung

Research output: Contribution to journalShort survey

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5-13
Number of pages9
JournalBMB reports
Volume51
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

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Neurodegenerative diseases
Neurodegenerative Diseases
Poisons
Amyotrophic Lateral Sclerosis
Synucleins
Multifunctional Enzymes
Protein Disulfide-Isomerases
transglutaminase 2
Biochemistry
Prion Diseases
Prions
GTP Phosphohydrolases
Huntington Disease
DNA-Binding Proteins
Brain Diseases
Substrates
Amyloid
Protein Kinases
Parkinson Disease
Brain

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

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New insight into transglutaminase 2 and link to neurodegenerative diseases. / Min, Boram; Chung, Kwang Chul.

In: BMB reports, Vol. 51, No. 1, 01.01.2018, p. 5-13.

Research output: Contribution to journalShort survey

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