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Transglutaminases pp 283–314Cite as

Transglutaminases and Neurological Diseases

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Abstract

Transglutaminases, and predominantly transglutaminase 2 (TG2), have been implicated in the pathogenesis of a number of neurological conditions. In the context of older-age onset neurodegenerative diseases that are characterized by protein aggregates, it was initially postulated that transglutaminases contributed to the pathogenic process by crosslinking and facilitating aggregate formation. However, more recent studies have provided evidence that although TG2, and possibly other transglutaminases, likely contribute to the progression of certain neurodegenerative diseases, this probably does not involve crosslinking and the formation of insoluble protein aggregates. Indeed, there is growing evidence that TG2 could be a contributing factor in neurological diseases through mechanisms such as modulating transcriptional events, affecting cell migration and adhesion, or altering cellular differentiation processes. In this chapter, neurological diseases in which transglutaminases have been implicated as a contributing factor are discussed. The chapter will conclude with a discussion about cystamine, a non-specific in vitro inhibitor of transglutaminases, as a neuroprotective agent.

These authors contribute equally to this chapter.

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References

  • Ajroud-Driss S, Siddique T (2014) Sporadic and hereditary amyotrophic lateral sclerosis (ALS). Biochim Biophys Acta 1852:679–684

    Article  PubMed  CAS  Google Scholar 

  • Akar N, Donmez B, Deda G (2007) FXIII gene Val34Leu polymorphism in Turkish children with cerebral infarct. J Child Neurol 22:222–224

    Article  PubMed  Google Scholar 

  • Almeida RD, Manadas BJ, Melo CV, Gomes JR, Mendes CS, Graos MM, Carvalho RF, Carvalho AP, Duarte CB (2005) Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways. Cell Death Differ 12:1329–1343

    Article  CAS  PubMed  Google Scholar 

  • Appelt DM, Balin BJ (1997) The association of tissue transglutaminase with human recombinant tau results in the formation of insoluble filamentous structures. Brain Res 745:21–31

    Article  CAS  PubMed  Google Scholar 

  • Bailey CD, Johnson GV (2005) Tissue transglutaminase contributes to disease progression in the R6/2 Huntington’s disease mouse model via aggregate-independent mechanisms. J Neurochem 92:83–92

    Article  CAS  PubMed  Google Scholar 

  • Bailey CD, Johnson GV (2006) The protective effects of cystamine in the R6/2 Huntington’s disease mouse involve mechanisms other than the inhibition of tissue transglutaminase. Neurobiol Aging 27:871–879

    Article  CAS  PubMed  Google Scholar 

  • Basso M, Berlin J, Xia L, Sleiman SF, Ko B, Haskew-Layton R, Kim E, Antonyak MA, Cerione RA, Iismaa SE, Willis D, Cho S, Ratan RR (2012) Transglutaminase inhibition protects against oxidative stress-induced neuronal death downstream of pathological ERK activation. J Neurosci 32:6561–6569

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bates GP, Mangiarini L, Wanker EE, Davies SW (1998) Polyglutamine expansion and Huntington’s disease. Biochem Soc Trans 26:471–475

    Article  CAS  PubMed  Google Scholar 

  • Bonelli RM, Aschoff A, Niederwieser G, Heuberger C, Jirikowski G (2002) Cerebrospinal fluid tissue transglutaminase as a biochemical marker for Alzheimer’s disease. Neurobiol Dis 11:106–110

    Article  CAS  PubMed  Google Scholar 

  • Borrell-Pages M, Canals JM, Cordelieres FP, Parker JA, Pineda JR, Grange G, Bryson EA, Guillermier M, Hirsch E, Hantraye P, Cheetham ME, Neri C, Alberch J, Brouillet E, Saudou F, Humbert S (2006) Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase. J Clin Invest 116:1410–1424

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bousquet M, Gibrat C, Ouellet M, Rouillard C, Calon F, Cicchetti F (2010) Cystamine metabolism and brain transport properties: clinical implications for neurodegenerative diseases. J Neurochem 114:1651–1658

    Article  CAS  PubMed  Google Scholar 

  • Catto AJ, Kohler HP, Bannan S, Stickland M, Carter A, Grant PJ (1998) Factor XIII Val 34 Leu: a novel association with primary intracerebral hemorrhage. Stroke 29:813–816

    Article  CAS  PubMed  Google Scholar 

  • Chen A, Xiong LJ, Tong Y, Mao M (2013) The neuroprotective roles of BDNF in hypoxic ischemic brain injury. Biomed Rep 1:167–176

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chun W, Lesort M, Tucholski J, Ross CA, Johnson GV (2001) Tissue transglutaminase does not contribute to the formation of mutant huntingtin aggregates. J Cell Biol 153:25–34

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Citron BA, Santacruz KS, Davies PJ, Festoff BW (2001) Intron-exon swapping of transglutaminase mRNA and neuronal Tau aggregation in Alzheimer’s disease. J Biol Chem 276:3295–3301

    Article  CAS  PubMed  Google Scholar 

  • Colak G, Johnson GV (2012) Complete transglutaminase 2 ablation results in reduced stroke volumes and astrocytes that exhibit increased survival in response to ischemia. Neurobiol Dis 45:1042–1050

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Colak G, Keillor JW, Johnson GV (2011) Cytosolic guanine nucledotide binding deficient form of transglutaminase 2 (R580a) potentiates cell death in oxygen glucose deprivation. PLoS One 6:e16665

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cooper AJ, Sheu KF, Burke JR, Onodera O, Strittmatter WJ, Roses AD, Blass JP (1997) Polyglutamine domains are substrates of tissue transglutaminase: does transglutaminase play a role in expanded CAG/poly-Q neurodegenerative diseases? J Neurochem 69:431–434

    Article  CAS  PubMed  Google Scholar 

  • Dawson TM, Dawson VL (2003) Molecular pathways of neurodegeneration in Parkinson’s disease. Science 302:819–822

    Article  CAS  PubMed  Google Scholar 

  • de Cristofaro T, Affaitati A, Cariello L, Avvedimento EV, Varrone S (1999) The length of polyglutamine tract, its level of expression, the rate of degradation, and the transglutaminase activity influence the formation of intracellular aggregates. Biochem Biophys Res Commun 260:150–158

    Article  PubMed  Google Scholar 

  • de Jager M, van der Wildt B, Schul E, Bol JG, van Duinen SG, Drukarch B, Wilhelmus MM (2013) Tissue transglutaminase colocalizes with extracellular matrix proteins in cerebral amyloid angiopathy. Neurobiol Aging 34:1159–1169

    Article  PubMed  CAS  Google Scholar 

  • de Vivo G, di Lorenzo R, Ricotta M, Gentile V (2009) Role of the transglutaminase enzymes in the nervous system and their possible involvement in neurodegenerative diseases. Curr Med Chem 16:4767–4773

    Article  PubMed  Google Scholar 

  • Dedeoglu A, Kubilus JK, Jeitner TM, Matson SA, Bogdanov M, Kowall NW, Matson WR, Cooper AJ, Ratan RR, Beal MF, Hersch SM, Ferrante RJ (2002) Therapeutic effects of cystamine in a murine model of Huntington’s disease. J Neurosci 22:8942–8950

    CAS  PubMed  Google Scholar 

  • D’Souza DR, Wei J, Shao Q, Hebert MD, Subramony SH, Vig PJ (2006) Tissue transglutaminase crosslinks ataxin-1: possible role in SCA1 pathogenesis. Neurosci Lett 409:5–9

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Dudek SM, Johnson GV (1993) Transglutaminase catalyzes the formation of sodium dodecyl sulfate-insoluble, Alz-50-reactive polymers of tau. J Neurochem 61:1159–1162

    Article  CAS  PubMed  Google Scholar 

  • Dudek SM, Johnson GV (1994) Transglutaminase facilitates the formation of polymers of the beta-amyloid peptide. Brain Res 651:129–133

    Article  CAS  PubMed  Google Scholar 

  • Dyer LM, Schooler KP, Ai L, Klop C, Qiu J, Robertson KD, Brown KD (2011) The transglutaminase 2 gene is aberrantly hypermethylated in glioma. J Neurooncol 101:429–440

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Eitan S, Solomon A, Lavie V, Yoles E, Hirschberg DL, Belkin M, Schwartz M (1994) Recovery of visual response of injured adult rat optic nerves treated with transglutaminase. Science 264:1764–1768

    Article  CAS  PubMed  Google Scholar 

  • Elbaz A, Poirier O, Canaple S, Chedru F, Cambien F, Amarenco P (2000) The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction. Blood 95:586–591

    CAS  PubMed  Google Scholar 

  • Endler G, Funk M, Haering D, Lalouschek W, Lang W, Mirafzal M, Wagner O, Mannhalter C (2003) Is the factor XIII 34Val/Leu polymorphism a protective factor for cerebrovascular disease? Br J Haematol 120:310–314

    Article  CAS  PubMed  Google Scholar 

  • Espitia Pinzon N, Stroo E, T Hart BA, Bol JG, Drukarch B, Bauer J, Van Dam AM (2014) Tissue transglutaminase in marmoset experimental multiple sclerosis: discrepancy between white and grey matter. PLoS One 9:e100574

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Festoff BW, Santacruz K, Arnold PM, Sebastian CT, Davies PJ, Citron BA (2002) Injury-induced “switch” from GTP-regulated to novel GTP-independent isoform of tissue transglutaminase in the rat spinal cord. J Neurochem 81:708–718

    Article  CAS  PubMed  Google Scholar 

  • Filiano AJ, Bailey CD, Tucholski J, Gundemir S, Johnson GV (2008) Transglutaminase 2 protects against ischemic insult, interacts with HIF1beta, and attenuates HIF1 signaling. FASEB J 22:2662–2675

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Filiano AJ, Tucholski J, Dolan PJ, Colak G, Johnson GV (2010) Transglutaminase 2 protects against ischemic stroke. Neurobiol Dis 39:334–343

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fox JH, Barber DS, Singh B, Zucker B, Swindell MK, Norflus F, Buzescu R, Chopra R, Ferrante RJ, Kazantsev A, Hersch SM (2004) Cystamine increases L-cysteine levels in Huntington’s disease transgenic mouse brain and in a PC12 model of polyglutamine aggregation. J Neurochem 91:413–422

    Article  CAS  PubMed  Google Scholar 

  • Fu J, Yang QY, Sai K, Chen FR, Pang JC, Ng HK, Kwan AL, Chen ZP (2013) TGM2 inhibition attenuates ID1 expression in CD44-high glioma-initiating cells. Neuro Oncol 15:1353–1365

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fujita K, Ando M, Yamauchi M, Nagata Y, Honda M (1995) Alteration of transglutaminase activity in rat and human spinal cord after neuronal degeneration. Neurochem Res 20:1195–1201

    Article  CAS  PubMed  Google Scholar 

  • Fujita K, Honda M, Hayashi R, Ogawa K, Ando M, Yamauchi M, Nagata Y (1998a) Transglutaminase activity in serum and cerebrospinal fluid in sporadic amyotrophic lateral sclerosis: a possible use as an indicator of extent of the motor neuron loss. J Neurol Sci 158:53–57

    Article  CAS  PubMed  Google Scholar 

  • Fujita K, Shibayama K, Yamauchi M, Kato T, Ando M, Takahashi H, Iritani K, Yoshimoto N, Nagata Y (1998b) Alteration of enzymatic activities implicating neuronal degeneration in the spinal cord of the motor neuron degeneration mouse during postnatal development. Neurochem Res 23:557–562

    Article  CAS  PubMed  Google Scholar 

  • Fujita K, Kato T, Shibayama K, Imada H, Yamauchi M, Yoshimoto N, Miyachi E, Nagata Y (2006) Protective effect against 17beta-estradiol on neuronal apoptosis in hippocampus tissue following transient ischemia/recirculation in mongolian gerbils via down-regulation of tissue transglutaminase activity. Neurochem Res 31:1059–1068

    Article  CAS  PubMed  Google Scholar 

  • Gemmati D, Serino ML, Ongaro A, Tognazzo S, Moratelli S, Resca R, Moretti M, Scapoli GL (2001) A common mutation in the gene for coagulation factor XIII-A (VAL34Leu): a risk factor for primary intracerebral hemorrhage is protective against atherothrombotic diseases. Am J Hematol 67:183–188

    Article  CAS  PubMed  Google Scholar 

  • Gentile V, Sepe C, Calvani M, Melone MA, Cotrufo R, Cooper AJ, Blass JP, Peluso G (1998) Tissue transglutaminase-catalyzed formation of high-molecular-weight aggregates in vitro is favored with long polyglutamine domains: a possible mechanism contributing to CAG-triplet diseases. Arch Biochem Biophys 352:314–321

    Article  CAS  PubMed  Google Scholar 

  • Gibrat C, Cicchetti F (2011) Potential of cystamine and cysteamine in the treatment of neurodegenerative diseases. Prog Neuropsychopharmacol Biol Psychiatry 35:380–389

    Article  CAS  PubMed  Google Scholar 

  • Goldschmidt T, Antel J, Konig FB, Bruck W, Kuhlmann T (2009) Remyelination capacity of the MS brain decreases with disease chronicity. Neurology 72:1914–1921

    Article  CAS  PubMed  Google Scholar 

  • Green H (1993) Human genetic diseases due to codon reiteration: relationship to an evolutionary mechanism. Cell 74:955–956

    Article  CAS  PubMed  Google Scholar 

  • Grosso H, Mouradian MM (2012) Transglutaminase 2: biology, relevance to neurodegenerative diseases and therapeutic implications. Pharmacol Ther 133:392–410

    Article  CAS  PubMed  Google Scholar 

  • Grosso H, Woo JM, Lee KW, Im JY, Masliah E, Junn E, Mouradian MM (2014) Transglutaminase 2 exacerbates alpha-synuclein toxicity in mice and yeast. FASEB J 28:4280–4291

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM (1986a) Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem 261:6084–6089

    CAS  PubMed  Google Scholar 

  • Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI (1986b) Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A 83:4913–4917

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guan WJ, Wang JL, Liu YT, Ma YT, Zhou Y, Jiang H, Shen L, Guo JF, Xia K, Li JD, Tang BS (2013a) Spinocerebellar ataxia type 35 (SCA35)-associated transglutaminase 6 mutants sensitize cells to apoptosis. Biochem Biophys Res Commun 430:780–786

    Article  CAS  PubMed  Google Scholar 

  • Guan WJ, Xia KD, Ma YT, Liu YT, Shi YT, Jiang H, Shen L, Xia K, Li JD, Tang BS, Wang JL (2013b) Transglutaminase 6 interacts with polyQ proteins and promotes the formation of polyQ aggregates. Biochem Biophys Res Commun 437:94–100

    Article  CAS  PubMed  Google Scholar 

  • Gundemir S, Johnson GV (2009) Intracellular localization and conformational state of transglutaminase 2: implications for cell death. PLoS One 4:e6123

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gundemir S, Colak G, Tucholski J, Johnson GV (2012) Transglutaminase 2: a molecular Swiss army knife. Biochim Biophys Acta 1823:406–419

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gundemir S, Colak G, Feola J, Blouin R, Johnson GV (2013) Transglutaminase 2 facilitates or ameliorates HIF signaling and ischemic cell death depending on its conformation and localization. Biochim Biophys Acta 1833:1–10

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hadjivassiliou M, Aeschlimann P, Strigun A, Sanders DS, Woodroofe N, Aeschlimann D (2008) Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Ann Neurol 64:332–343

    Article  CAS  PubMed  Google Scholar 

  • Haigler HT, Maxfield FR, Willingham MC, Pastan I (1980) Dansylcadaverine inhibits internalization of 125I-epidermal growth factor in BALB 3T3 cells. J Biol Chem 255:1239–1241

    CAS  PubMed  Google Scholar 

  • Halverson RA, Lewis J, Frausto S, Hutton M, Muma NA (2005) Tau protein is cross-linked by transglutaminase in P301L tau transgenic mice. J Neurosci 25:1226–1233

    Article  CAS  PubMed  Google Scholar 

  • Hartley DM, Zhao C, Speier AC, Woodard GA, Li S, Li Z, Walz T (2008) Transglutaminase induces protofibril-like amyloid beta-protein assemblies that are protease-resistant and inhibit long-term potentiation. J Biol Chem 283:16790–16800

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hilton DA, Love S, Barber R (1997) Increased endothelial expression of transglutaminase in glioblastomas. Neuropathol Appl Neurobiol 23:507–511

    Article  CAS  PubMed  Google Scholar 

  • Ho GJ, Gregory EJ, Smirnova IV, Zoubine MN, Festoff BW (1994) Cross-linking of beta-amyloid protein precursor catalyzed by tissue transglutaminase. FEBS Lett 349:151–154

    Article  CAS  PubMed  Google Scholar 

  • Hohsfield LA, Daschil N, Oradd G, Stromberg I, Humpel C (2014) Vascular pathology of 20-month-old hypercholesterolemia mice in comparison to triple-transgenic and APPSwDI Alzheimer’s disease mouse models. Mol Cell Neurosci 63:83–95

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Holmes FE, Haynes LW (1996) Superactivation of transglutaminase type 2 without change in enzyme level occurs during progressive neurodegeneration in the mnd mouse mutant. Neurosci Lett 213:185–188

    Article  CAS  PubMed  Google Scholar 

  • Huang YC, Wei KC, Chang CN, Chen PY, Hsu PW, Chen CP, Lu CS, Wang HL, Gutmann DH, Yeh TH (2014) Transglutaminase 2 expression is increased as a function of malignancy grade and negatively regulates cell growth in meningioma. PLoS One 9:e108228

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hwang IK, Yoo KY, Yi SS, Kim IY, Hwang HS, Lee KY, Choi SM, Lee IS, Yoon YS, Kim SY, Won MH, Seong JK (2009) Expression of tissue-type transglutaminase (tTG) and the effect of tTG inhibitor on the hippocampal CA1 region after transient ischemia in gerbils. Brain Res 1263:134–142

    Article  CAS  PubMed  Google Scholar 

  • Ientile R, Caccamo D, Marciano MC, Curro M, Mannucci C, Campisi A, Calapai G (2004) Transglutaminase activity and transglutaminase mRNA transcripts in gerbil brain ischemia. Neurosci Lett 363:173–177

    Article  CAS  PubMed  Google Scholar 

  • Igarashi S, Koide R, Shimohata T, Yamada M, Hayashi Y, Takano H, Date H, Oyake M, Sato T, Sato A, Egawa S, Ikeuchi T, Tanaka H, Nakano R, Tanaka K, Hozumi I, Inuzuka T, Takahashi H, Tsuji S (1998) Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch. Nat Genet 18:111–117

    Article  CAS  PubMed  Google Scholar 

  • Ikura K, Takahata K, Sasaki R (1993) Cross-linking of a synthetic partial-length (1–28) peptide of the Alzheimer beta/A4 amyloid protein by transglutaminase. FEBS Lett 326:109–111

    Article  CAS  PubMed  Google Scholar 

  • Iniesta JA, Corral J, Gonzalez-Conejero R, Diaz Ortuno A, Martinez Navarro ML, Vicente V (2001) Role of factor XIII Val 34 Leu polymorphism in patients with migraine. Cephalalgia 21:837–841

    Article  CAS  PubMed  Google Scholar 

  • Jeitner TM, Bogdanov MB, Matson WR, Daikhin Y, Yudkoff M, Folk JE, Steinman L, Browne SE, Beal MF, Blass JP, Cooper AJ (2001) N(epsilon)-(gamma-L-glutamyl)-L-lysine (GGEL) is increased in cerebrospinal fluid of patients with Huntington’s disease. J Neurochem 79:1109–1112

    Article  CAS  PubMed  Google Scholar 

  • Jeitner TM, Delikatny EJ, Ahlqvist J, Capper H, Cooper AJ (2005) Mechanism for the inhibition of transglutaminase 2 by cystamine. Biochem Pharmacol 69:961–970

    Article  CAS  PubMed  Google Scholar 

  • Jeitner TM, Matson WR, Folk JE, Blass JP, Cooper AJ (2008) Increased levels of gamma-glutamylamines in Huntington disease CSF. J Neurochem 106:37–44

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Johnson GV, Leshoure R Jr (2004) Immunoblot analysis reveals that isopeptide antibodies do not specifically recognize the epsilon-(gamma-glutamyl)lysine bonds formed by transglutaminase activity. J Neurosci Methods 134:151–158

    Article  CAS  PubMed  Google Scholar 

  • Johnson GV, Cox TM, Lockhart JP, Zinnerman MD, Miller ML, Powers RE (1997) Transglutaminase activity is increased in Alzheimer’s disease brain. Brain Res 751:323–329

    Article  CAS  PubMed  Google Scholar 

  • Junn E, Ronchetti RD, Quezado MM, Kim SY, Mouradian MM (2003) Tissue transglutaminase-induced aggregation of alpha-synuclein: Implications for Lewy body formation in Parkinson’s disease and dementia with Lewy bodies. Proc Natl Acad Sci U S A 100:2047–2052

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kahlem P, Terre C, Green H, Djian P (1996) Peptides containing glutamine repeats as substrates for transglutaminase-catalyzed cross-linking: relevance to diseases of the nervous system. Proc Natl Acad Sci U S A 93:14580–14585

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kahlem P, Green H, Djian P (1998) Transglutaminase action imitates Huntington’s disease: selective polymerization of Huntingtin containing expanded polyglutamine. Mol Cell 1:595–601

    Article  CAS  PubMed  Google Scholar 

  • Kain K, Bamford J, Bavington J, Young J, Catto AJ (2005) Factor XIII--circulating levels and Val34Leu polymorphism in relatives of South Asian patients with ischemic stroke. J Thromb Haemost 3:171–173

    Article  CAS  PubMed  Google Scholar 

  • Karpuj MV, Garren H, Slunt H, Price DL, Gusella J, Becher MW, Steinman L (1999) Transglutaminase aggregates huntingtin into nonamyloidogenic polymers, and its enzymatic activity increases in Huntington’s disease brain nuclei. Proc Natl Acad Sci U S A 96:7388–7393

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Karpuj MV, Becher MW, Springer JE, Chabas D, Youssef S, Pedotti R, Mitchell D, Steinman L (2002) Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine. Nat Med 8:143–149

    Article  CAS  PubMed  Google Scholar 

  • Kawabe K, Takano K, Moriyama M, Nakamura Y (2014) Lipopolysaccharide-Stimulated Transglutaminase 2 Expression Enhances Endocytosis Activity in the Mouse Microglial Cell Line BV-2. Neuroimmunomodulation 22:243–249

    Article  PubMed  CAS  Google Scholar 

  • Kim SY, Grant P, Lee JH, Pant HC, Steinert PM (1999) Differential expression of multiple transglutaminases in human brain. Increased expression and cross-linking by transglutaminases 1 and 2 in Alzheimer’s disease. J Biol Chem 274:30715–30721

    Article  CAS  PubMed  Google Scholar 

  • Kim C, Lee HC, Sung JJ (2014) Amyotrophic lateral sclerosis – cell based therapy and novel therapeutic development. Exp Neurobiol 23:207–214

    Article  PubMed Central  PubMed  Google Scholar 

  • Kohler HP, Ariens RA, Catto AJ, Carter AM, Miller GJ, Cooper JA, Mansfield MW, Standeven KF, Grant PJ (2002) Factor XIII A-subunit concentration predicts outcome in stroke subjects and vascular outcome in healthy, middle-aged men. Br J Haematol 118:825–832

    Article  CAS  PubMed  Google Scholar 

  • Kovarova H, Pulpanova J (1979) Effect of cystamine on rat tissue GSH level and glutathione reductase activity. Strahlentherapie 155:875–878

    CAS  PubMed  Google Scholar 

  • Kumar A, Kneynsberg A, Tucholski J, Perry G, van Groen T, Detloff PJ, Lesort M (2012) Tissue transglutaminase overexpression does not modify the disease phenotype of the R6/2 mouse model of Huntington’s disease. Exp Neurol 237:78–89

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lai TS, Tucker T, Burke JR, Strittmatter WJ, Greenberg CS (2004) Effect of tissue transglutaminase on the solubility of proteins containing expanded polyglutamine repeats. J Neurochem 88:1253–1260

    Article  CAS  PubMed  Google Scholar 

  • Lesort M, Attanavanich K, Zhang J, Johnson GV (1998) Distinct nuclear localization and activity of tissue transglutaminase. J Biol Chem 273:11991–11994

    Article  CAS  PubMed  Google Scholar 

  • Lesort M, Chun W, Johnson GV, Ferrante RJ (1999) Tissue transglutaminase is increased in Huntington’s disease brain. J Neurochem 73:2018–2027

    CAS  PubMed  Google Scholar 

  • Lesort M, Tucholski J, Miller ML, Johnson GV (2000) Tissue transglutaminase: a possible role in neurodegenerative diseases. Prog Neurobiol 61:439–463

    Article  CAS  PubMed  Google Scholar 

  • Lesort M, Lee M, Tucholski J, Johnson GV (2003) Cystamine inhibits caspase activity. Implications for the treatment of polyglutamine disorders. J Biol Chem 278:3825–3830

    Article  CAS  PubMed  Google Scholar 

  • Li M, Pang SY, Song Y, Kung MH, Ho SL, Sham PC (2013) Whole exome sequencing identifies a novel mutation in the transglutaminase 6 gene for spinocerebellar ataxia in a Chinese family. Clin Genet 83:269–273

    Article  CAS  PubMed  Google Scholar 

  • Li P-C, Jiao Y, Ding J, Chen Y-C, Cui Y, Qian C, Yang X-Y, Ju S-H, Yao H-H, Teng G-J (2014) Cystamine improves functional recovery via axon remodeling and neuroprotection after stroke in mice. CNS Neurosci Ther 21:231–240

    Article  PubMed  CAS  Google Scholar 

  • Liu L, Belkadi A, Darnall L, Hu T, Drescher C, Cotleur AC, Padovani-Claudio D, He T, Choi K, Lane TE, Miller RH, Ransohoff RM (2010) CXCR2-positive neutrophils are essential for cuprizone-induced demyelination: relevance to multiple sclerosis. Nat Neurosci 13:319–326

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu YT, Tang BS, Lan W, Song NN, Huang Y, Zhang L, Guan WJ, Shi YT, Shen L, Jiang H, Guo JF, Xia K, Ding YQ, Wang JL (2013) Distribution of transglutaminase 6 in the central nervous system of adult mice. Anat Rec (Hoboken) 296:1576–1587

    Article  CAS  Google Scholar 

  • Lorand L, Graham RM (2003) Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol 4:140–156

    Article  CAS  PubMed  Google Scholar 

  • Mandrusiak LM, Beitel LK, Wang X, Scanlon TC, Chevalier-Larsen E, Merry DE, Trifiro MA (2003) Transglutaminase potentiates ligand-dependent proteasome dysfunction induced by polyglutamine-expanded androgen receptor. Hum Mol Genet 12:1497–1506

    Article  CAS  PubMed  Google Scholar 

  • Margulis BA, Vigont V, Lazarev VF, Kaznacheyeva EV, Guzhova IV (2013) Pharmacological protein targets in polyglutamine diseases: mutant polypeptides and their interactors. FEBS Lett 587:1997–2007

    Article  CAS  PubMed  Google Scholar 

  • Mastroberardino PG, Iannicola C, Nardacci R, Bernassola F, de Laurenzi V, Melino G, Moreno S, Pavone F, Oliverio S, Fesus L, Piacentini M (2002) ‘Tissue’ transglutaminase ablation reduces neuronal death and prolongs survival in a mouse model of Huntington’s disease. Cell Death Differ 9:873–880

    Article  CAS  PubMed  Google Scholar 

  • Mcconoughey SJ, Basso M, Niatsetskaya ZV, Sleiman SF, Smirnova NA, Langley BC, Mahishi L, Cooper AJ, Antonyak MA, Cerione RA, Li B, Starkov A, Chaturvedi RK, Beal MF, Coppola G, Geschwind DH, Ryu H, Xia L, Iismaa SE, Pallos J, Pasternack R, Hils M, Fan J, Raymond LA, Marsh JL, Thompson LM, Ratan RR (2010) Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington disease. EMBO Mol Med 2:349–370

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Menalled LB, Kudwa AE, Oakeshott S, Farrar A, Paterson N, Filippov I, Miller S, Kwan M, Olsen M, Beltran J, Torello J, Fitzpatrick J, Mushlin R, Cox K, Mcconnell K, Mazzella M, He D, Osborne GF, Al-Nackkash R, Bates GP, Tuunanen P, Lehtimaki K, Brunner D, Ghavami A, Ramboz S, Park L, Macdonald D, Munoz-Sanjuan I, Howland D (2014) Genetic deletion of transglutaminase 2 does not rescue the phenotypic deficits observed in R6/2 and zQ175 mouse models of Huntington’s disease. PLoS One 9:e99520

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Milakovic T, Tucholski J, Mccoy E, Johnson GV (2004) Intracellular localization and activity state of tissue transglutaminase differentially impacts cell death. J Biol Chem 279:8715–8722

    Article  CAS  PubMed  Google Scholar 

  • Miller CC, Anderton BH (1986) Transglutaminase and the neuronal cytoskeleton in Alzheimer’s disease. J Neurochem 46:1912–1922

    Article  CAS  PubMed  Google Scholar 

  • Miller ML, Johnson GV (1995) Transglutaminase cross-linking of the tau protein. J Neurochem 65:1760–1770

    Article  CAS  PubMed  Google Scholar 

  • Monsonego A, Shani Y, Friedmann I, Paas Y, Eizenberg O, Schwartz M (1997) Expression of GTP-dependent and GTP-independent tissue-type transglutaminase in cytokine-treated rat brain astrocytes. J Biol Chem 272:3724–3732

    Article  CAS  PubMed  Google Scholar 

  • Munsie L, Caron N, Atwal RS, Marsden I, Wild EJ, Bamburg JR, Tabrizi SJ, Truant R (2011) Mutant huntingtin causes defective actin remodeling during stress: defining a new role for transglutaminase 2 in neurodegenerative disease. Hum Mol Genet 20:1937–1951

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Murthy SN, Wilson JH, Lukas TJ, Kuret J, Lorand L (1998) Cross-linking sites of the human tau protein, probed by reactions with human transglutaminase. J Neurochem 71:2607–2614

    Article  CAS  PubMed  Google Scholar 

  • Nanda N, Iismaa SE, Owens WA, Husain A, Mackay F, Graham RM (2001) Targeted inactivation of Gh/tissue transglutaminase II. J Biol Chem 276:20673–20678

    Article  CAS  PubMed  Google Scholar 

  • Nemes Z, Devreese B, Steinert PM, van Beeumen J, Fesus L (2004) Cross-linking of ubiquitin, HSP27, parkin, and alpha-synuclein by gamma-glutamyl-epsilon-lysine bonds in Alzheimer’s neurofibrillary tangles. FASEB J 18:1135–1137

    CAS  PubMed  Google Scholar 

  • Nilsson JL, Stenberg P, Ljunggren C, Eriksson O, Lunden R (1971) Fibrin-stabilizing factor inhibitors. 3. Sulphonamides related to monodansylcadaverine. Acta Pharm Suec 8:497–504

    CAS  PubMed  Google Scholar 

  • Nurminskaya MV, Belkin AM (2012) Cellular functions of tissue transglutaminase. Int Rev Cell Mol Biol 294:1–97

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Obara Y, Yanagihata Y, Abe T, Dafik L, Ishii K, Nakahata N (2013) Galpha(h)/transglutaminase-2 activity is required for maximal activation of adenylylcyclase 8 in human and rat glioma cells. Cell Signal 25:589–597

    Article  CAS  PubMed  Google Scholar 

  • Okauchi M, Xi G, Keep RF, Hua Y (2009) Tissue-type transglutaminase and the effects of cystamine on intracerebral hemorrhage-induced brain edema and neurological deficits. Brain Res 1249:229–236

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Oono M, Okado-Matsumoto A, Shodai A, Ido A, Ohta Y, Abe K, Ayaki T, Ito H, Takahashi R, Taniguchi N, Urushitani M (2014) Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through interaction with misfolded superoxide dismutase 1. J Neurochem 128:403–418

    Article  CAS  PubMed  Google Scholar 

  • Organization WH (2002) The world health report. WHO, Geneva

    Google Scholar 

  • Pinto JT, van Raamsdonk JM, Leavitt BR, Hayden MR, Jeitner TM, Thaler HT, Krasnikov BF, Cooper AJ (2005) Treatment of YAC128 mice and their wild-type littermates with cystamine does not lead to its accumulation in plasma or brain: implications for the treatment of Huntington disease. J Neurochem 94:1087–1101

    Article  CAS  PubMed  Google Scholar 

  • Prins M, Eriksson C, Wierinckx A, Bol JG, Binnekade R, Tilders FJ, van Dam AM (2013) Interleukin-1beta and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis. PLoS One 8:e83835

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rasmussen LK, Sorensen ES, Petersen TE, Gliemann J, Jensen PH (1994) Identification of glutamine and lysine residues in Alzheimer amyloid beta A4 peptide responsible for transglutaminase-catalysed homopolymerization and cross-linking to alpha 2M receptor. FEBS Lett 338:161–166

    Article  CAS  PubMed  Google Scholar 

  • Reiner AP, Frank MB, Schwartz SM, Linenberger ML, Longstreth WT, Teramura G, Rosendaal FR, Psaty BM, Siscovick DS (2002) Coagulation factor XIII polymorphisms and the risk of myocardial infarction and ischaemic stroke in young women. Br J Haematol 116:376–382

    Article  CAS  PubMed  Google Scholar 

  • Ruan Q, Quintanilla RA, Johnson GV (2007) Type 2 transglutaminase differentially modulates striatal cell death in the presence of wild type or mutant huntingtin. J Neurochem 102:25–36

    Article  CAS  PubMed  Google Scholar 

  • Sato K, Murakami T, Hamakawa Y, Kamada H, Nagano I, Shoji M, Takata H, Nobukuni K, Ihara Y, Namba R, Hayabara T, Hirose S, Abe K (2002) Selective colocalization of transglutaminase-like activity in ubiquitinated intranuclear inclusions of hereditary dentatorubral-pallidoluysian atrophy. Brain Res 952:327–330

    Article  CAS  PubMed  Google Scholar 

  • Schmid AW, Chiappe D, Pignat V, Grimminger V, Hang I, Moniatte M, Lashuel HA (2009) Dissecting the mechanisms of tissue transglutaminase-induced cross-linking of alpha-synuclein: implications for the pathogenesis of Parkinson disease. J Biol Chem 284:13128–13142

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Segers-Nolten IM, Wilhelmus MM, Veldhuis G, van Rooijen BD, Drukarch B, Subramaniam V (2008) Tissue transglutaminase modulates alpha-synuclein oligomerization. Protein Sci 17:1395–1402

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Selkoe DJ, Abraham C, Ihara Y (1982) Brain transglutaminase: in vitro crosslinking of human neurofilament proteins into insoluble polymers. Proc Natl Acad Sci U S A 79:6070–6074

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Singer SM, Zainelli GM, Norlund MA, Lee JM, Muma NA (2002) Transglutaminase bonds in neurofibrillary tangles and paired helical filament tau early in Alzheimer’s disease. Neurochem Int 40:17–30

    Article  CAS  PubMed  Google Scholar 

  • Slow EJ, van Raamsdonk J, Rogers D, Coleman SH, Graham RK, Deng Y, Oh R, Bissada N, Hossain SM, Yang YZ, Li XJ, Simpson EM, Gutekunst CA, Leavitt BR, Hayden MR (2003) Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum Mol Genet 12:1555–1567

    Article  CAS  PubMed  Google Scholar 

  • Tetzlaff W, Gilad VH, Leonard C, Bisby MA, Gilad GM (1988) Retrograde changes in transglutaminase activity after peripheral nerve injuries. Brain Res 445:142–146

    Article  CAS  PubMed  Google Scholar 

  • Todd TW, Lim J (2013) Aggregation formation in the polyglutamine diseases: protection at a cost? Mol Cells 36:185–194

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tolentino PJ, Deford SM, Notterpek L, Glenn CC, Pike BR, Wang KK, Hayes RL (2002) Up-regulation of tissue-type transglutaminase after traumatic brain injury. J Neurochem 80:579–588

    Article  CAS  PubMed  Google Scholar 

  • Tolentino PJ, Waghray A, Wang KK, Hayes RL (2004) Increased expression of tissue-type transglutaminase following middle cerebral artery occlusion in rats. J Neurochem 89:1301–1307

    Article  CAS  PubMed  Google Scholar 

  • Tucholski J, Roth KA, Johnson GV (2006) Tissue transglutaminase overexpression in the brain potentiates calcium-induced hippocampal damage. J Neurochem 97:582–594

    Article  CAS  PubMed  Google Scholar 

  • van Raamsdonk JM, Pearson J, Bailey CD, Rogers DA, Johnson GV, Hayden MR, Leavitt BR (2005) Cystamine treatment is neuroprotective in the YAC128 mouse model of Huntington disease. J Neurochem 95:210–220

    Article  PubMed  CAS  Google Scholar 

  • van Strien ME, Baron W, Bakker EN, Bauer J, Bol JG, Breve JJ, Binnekade R, van der Laarse WJ, Drukarch B, van Dam AM (2011a) Tissue transglutaminase activity is involved in the differentiation of oligodendrocyte precursor cells into myelin-forming oligodendrocytes during CNS remyelination. Glia 59:1622–1634

    Article  PubMed  Google Scholar 

  • van Strien ME, Breve JJ, Fratantoni S, Schreurs MW, Bol JG, Jongenelen CA, Drukarch B, van Dam AM (2011b) Astrocyte-derived tissue transglutaminase interacts with fibronectin: a role in astrocyte adhesion and migration? PLoS One 6:e25037

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • van Strien ME, Drukarch B, Bol JG, van der Valk P, van Horssen J, Gerritsen WH, Breve JJ, van Dam AM (2011c) Appearance of tissue transglutaminase in astrocytes in multiple sclerosis lesions: a role in cell adhesion and migration? Brain Pathol 21:44–54

    Article  PubMed  CAS  Google Scholar 

  • Verhaar R, Jongenelen CA, Gerard M, Baekelandt V, van Dam AM, Wilhelmus MM, Drukarch B (2011) Blockade of enzyme activity inhibits tissue transglutaminase-mediated transamidation of alpha-synuclein in a cellular model of Parkinson’s disease. Neurochem Int 58:785–793

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Sarkar A, Cicchetti F, Yu M, Zhu A, Jokivarsi K, Saint-Pierre M, Brownell AL (2005) Cerebral PET imaging and histological evidence of transglutaminase inhibitor cystamine induced neuroprotection in transgenic R6/2 mouse model of Huntington’s disease. J Neurol Sci 231:57–66

    Article  CAS  PubMed  Google Scholar 

  • Wang JL, Yang X, Xia K, Hu ZM, Weng L, Jin X, Jiang H, Zhang P, Shen L, Guo JF, Li N, Li YR, Lei LF, Zhou J, Du J, Zhou YF, Pan Q, Wang J, Wang J, Li RQ, Tang BS (2010a) TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain 133:3510–3518

    Article  PubMed  Google Scholar 

  • Wang Z, Collighan RJ, Gross SR, Danen EH, Orend G, Telci D, Griffin M (2010b) RGD-independent cell adhesion via a tissue transglutaminase-fibronectin matrix promotes fibronectin fibril deposition and requires syndecan-4/2 alpha5beta1 integrin co-signaling. J Biol Chem 285:40212–40229

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Weber JJ, Sowa AS, Binder T, Hubener J (2014) From Pathways to Targets: Understanding the Mechanisms behind Polyglutamine Disease. Biomed Res Int 2014:701758

    PubMed Central  PubMed  Google Scholar 

  • Wilhelmus MM, Grunberg SC, Bol JG, van Dam AM, Hoozemans JJ, Rozemuller AJ, Drukarch B (2009) Transglutaminases and transglutaminase-catalyzed cross-links colocalize with the pathological lesions in Alzheimer’s disease brain. Brain Pathol 19:612–622

    Article  CAS  PubMed  Google Scholar 

  • Wilhelmus MM, Verhaar R, Andringa G, Bol JG, Cras P, Shan L, Hoozemans JJ, Drukarch B (2011) Presence of tissue transglutaminase in granular endoplasmic reticulum is characteristic of melanized neurons in Parkinson’s disease brain. Brain Pathol 21:130–139

    Article  CAS  PubMed  Google Scholar 

  • Wilhelmus MM, de Jager M, Drukarch B (2012a) Tissue transglutaminase: a novel therapeutic target in cerebral amyloid angiopathy. Neurodegener Dis 10:317–319

    Article  CAS  PubMed  Google Scholar 

  • Wilhelmus MM, de Jager M, Rozemuller AJ, Breve J, Bol JG, Eckert RL, Drukarch B (2012b) Transglutaminase 1 and its regulator tazarotene-induced gene 3 localize to neuronal tau inclusions in tauopathies. J Pathol 226:132–142

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wolf J, Jager C, Lachmann I, Schonknecht P, Morawski M, Arendt T, Mothes T (2013) Tissue transglutaminase is not a biochemical marker for Alzheimer’s disease. Neurobiol Aging 34:2495–2498

    Article  CAS  PubMed  Google Scholar 

  • Yuan L, Siegel M, Choi K, Khosla C, Miller CR, Jackson EN, Piwnica-Worms D, Rich KM (2007) Transglutaminase 2 inhibitor, KCC009, disrupts fibronectin assembly in the extracellular matrix and sensitizes orthotopic glioblastomas to chemotherapy. Oncogene 26:2563–2573

    Article  CAS  PubMed  Google Scholar 

  • Yuan L, Behdad A, Siegel M, Khosla C, Higashikubo R, Rich KM (2008) Tissue transgluaminase 2 expression in meningiomas. J Neurooncol 90:125–132

    Article  PubMed Central  PubMed  Google Scholar 

  • Yuan L, Holmes TC, Watts RE, Khosla C, Broekelmann TJ, Mecham R, Zheng H, Izaguirre EW, Rich KM (2011) Novel chemo-sensitizing agent, ERW1227B, impairs cellular motility and enhances cell death in glioblastomas. J Neurooncol 103:207–219

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zainelli GM, Ross CA, Troncoso JC, Muma NA (2003) Transglutaminase cross-links in intranuclear inclusions in Huntington disease. J Neuropathol Exp Neurol 62:14–24

    Article  CAS  PubMed  Google Scholar 

  • Zainelli GM, Dudek NL, Ross CA, Kim SY, Muma NA (2005) Mutant huntingtin protein: a substrate for transglutaminase 1, 2, and 3. J Neuropathol Exp Neurol 64:58–65

    Article  CAS  PubMed  Google Scholar 

  • Zemaitaitis MO, Lee JM, Troncoso JC, Muma NA (2000) Transglutaminase-induced cross-linking of tau proteins in progressive supranuclear palsy. J Neuropathol Exp Neurol 59:983–989

    Article  CAS  PubMed  Google Scholar 

  • Zemaitaitis MO, Kim SY, Halverson RA, Troncoso JC, Lee JM, Muma NA (2003) Transglutaminase activity, protein, and mRNA expression are increased in progressive supranuclear palsy. J Neuropathol Exp Neurol 62:173–184

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Pardridge WM (2001) Neuroprotection in transient focal brain ischemia after delayed intravenous administration of brain-derived neurotrophic factor conjugated to a blood-brain barrier drug targeting system. Stroke 32:1378–1384

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Johnson BR, Suri DE, Martinez J, Bjornsson TD (1998) Immunohistochemical demonstration of tissue transglutaminase in amyloid plaques. Acta Neuropathol 96:395–400

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Antonyak MA, Singh G, Cerione RA (2013) A mechanism for the upregulation of EGF receptor levels in glioblastomas. Cell Rep 3:2008–2020

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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    Authors and Affiliations

    1. Neuroscience Program, University of Rochester, Rochester, NY, 14642, USA

      Julianne Feola, Laura Yunes-Medina & Gail V. W. Johnson

    2. Department of Pharmacology and Physiology, University of Rochester, Rochester, NY, 14642, USA

      Alina Monteagudo & Gail V. W. Johnson

    3. Department of Anesthesiology, University of Rochester, Rochester, NY, 14642, USA

      Gail V. W. Johnson

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    1. Julianne Feola
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    2. Alina Monteagudo
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    3. Laura Yunes-Medina
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    4. Gail V. W. Johnson
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    Correspondence to Gail V. W. Johnson .

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    Editors and Affiliations

    1. Grad Sch of Pharmaceutical Sciences, Nagoya University, Nagoya, Aichi, Japan

      Kiyotaka Hitomi

    2. Micro-Signaling Regulation Technol. Unit, RIKEN Center for Life Sci. Technologies, Wako, Saitama, Japan

      Soichi Kojima

    3. Dept. Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary

      Laszlo Fesus

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    Feola, J., Monteagudo, A., Yunes-Medina, L., Johnson, G.V.W. (2015). Transglutaminases and Neurological Diseases. In: Hitomi, K., Kojima, S., Fesus, L. (eds) Transglutaminases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55825-5_13

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