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Review

Transglutaminase 2 as a therapeutic target for neurological conditions

& ORCID Icon
Pages 721-731 | Received 21 Jul 2021, Accepted 01 Oct 2021, Published online: 15 Oct 2021

References

  • Quinn BR, Yunes-Medina L, Johnson GVW. Transglutaminase 2: friend or foe? The discordant role in neurons and astrocytes. J Neurosci Res. 2018 Jul;96(7):1150–1158.
  • Eckert RL, Kaartinen MT, Nurminskaya M, et al. Transglutaminase regulation of cell function. Physiol Rev. 2014 Apr;94(2):383–417.
  • Gundemir S, Colak G, Tucholski J, et al. Transglutaminase 2: a molecular Swiss army knife. Biochim Biophys Acta. 2012 Feb;1823(2):406–419.
  • Karpuj MV, Becher MW, Steinman L. Evidence for a role for transglutaminase in Huntington’s disease and the potential therapeutic implications. Neurochem Int. 2002 Jan;40(1):31–36.
  • Lesort M, Chun W, Johnson GV, et al. Tissue transglutaminase is increased in Huntington’s disease brain. J Neurochem. 1999 Nov;73(5):2018–2027.
  • Citron BA, SantaCruz KS, Davies PJ, et al. Intron-exon swapping of transglutaminase mRNA and neuronal Tau aggregation in Alzheimer’s disease. J Biol Chem. 2001 Feb 2;276(5):3295–3301.
  • Johnson GV, Cox TM, Lockhart JP, et al. Transglutaminase activity is increased in Alzheimer’s disease brain. Brain Res. 1997 Mar 21;751(2):323–329.
  • Andringa G, Lam KY, Chegary M, et al. Tissue transglutaminase catalyzes the formation of alpha-synuclein crosslinks in Parkinson’s disease. FASEB J. 2004 May;18(7):932–934.
  • Junn E, Ronchetti RD, Quezado MM, et al. 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. 2003 Feb 18;100(4):2047–2052.
  • Wilhelmus MM, Verhaar R, Andringa G, et al. Presence of tissue transglutaminase in granular endoplasmic reticulum is characteristic of melanized neurons in Parkinson’s disease brain. Brain Pathol. 2011 Mar;21(2):130–139.
  • Festoff BW, SantaCruz K, Arnold PM, et al. Injury-induced “switch” from GTP-regulated to novel GTP-independent isoform of tissue transglutaminase in the rat spinal cord. J Neurochem. 2002 May;81(4):708–718.
  • Tolentino PJ, DeFord SM, Notterpek L, et al. Up-regulation of tissue-type transglutaminase after traumatic brain injury. J Neurochem. 2002 Feb;80(4):579–588.
  • Tolentino PJ, Waghray A, Wang KK, et al. Increased expression of tissue-type transglutaminase following middle cerebral artery occlusion in rats. J Neurochem. 2004 Jun;89(5):1301–1307.
  • van Strien ME, De Vries HE, Chrobok NL, et al. Tissue Transglutaminase contributes to experimental multiple sclerosis pathogenesis and clinical outcome by promoting macrophage migration. Brain Behav Immun. 2015;50:141–154.
  • van Strien ME, Drukarch B, Bol JG, et al. Appearance of tissue transglutaminase in astrocytes in multiple sclerosis lesions: a role in cell adhesion and migration? Brain Pathol. 2011 Jan;21(1):44–54.
  • Lu S, Saydak M, Gentile V, et al. Isolation and characterization of the human tissue transglutaminase gene promoter. J Biol Chem. 1995 Apr 28;270(17):9748–9756.
  • Jang GY, Jeon JH, Cho SY, et al. Transglutaminase 2 suppresses apoptosis by modulating caspase 3 and NF-kappaB activity in hypoxic tumor cells. Oncogene. 2010 Jan 21;29(3):356–367.
  • Monsonego A, Shani Y, Friedmann I, et al. Expression of GTP-dependent and GTP-independent tissue-type transglutaminase in cytokine-treated rat brain astrocytes. J Biol Chem. 1997 Feb 7;272(6):3724–3732.
  • Tucholski J, Roth KA, Johnson GV. Tissue transglutaminase overexpression in the brain potentiates calcium-induced hippocampal damage. J Neurochem. 2006 Apr;97(2):582–594.
  • Filiano AJ, Tucholski J, Dolan PJ, et al. Transglutaminase 2 protects against ischemic stroke. Neurobiol Dis. 2010 Sep;39(3):334–343.
  • Colak G, Johnson GV. Complete transglutaminase 2 ablation results in reduced stroke volumes and astrocytes that exhibit increased survival in response to ischemia. Neurobiol Dis. 2012 Mar;45(3):1042–1050.
  • Monteagudo A, Feola J, Natola H, et al. Depletion of astrocytic transglutaminase 2 improves injury outcomes. Mol Cell Neurosci. 2018 Oct;92:128–136.
  • Lorand L, Graham RM. Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol. 2003 Feb;4(2):140–156.
  • Keillor JW, Clouthier CM, Apperley KYP, et al. Acyl transfer mechanisms of tissue transglutaminase. Bioorg Chem. 2014;57:186–197.
  • Achyuthan KE, Greenberg CS. Identification of a guanosine triphosphate-binding site on Guinea pig liver transglutaminase. Role of GTP and calcium ions in modulating activity. J Biol Chem. 1987 Feb 5;262(4):1901–1906.
  • Stamnaes J, Pinkas DM, Fleckenstein B, et al. Redox regulation of transglutaminase 2 activity. J Biol Chem. 2010 Aug 13;285(33):25402–25409.
  • Jang TH, Park HH. Crystallization and preliminary X-ray crystallographic studies of transglutaminase 2 in complex with Ca2+. Acta Crystallogr F Struct Biol Commun. 2014 Apr;70(Pt 4):513–516.
  • Liu S, Cerione RA, Clardy J. Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity. Proc Natl Acad Sci U S A. 2002 Mar 5; 99(5):2743–2747.
  • Pinkas DM, Strop P, Brunger AT, et al. Transglutaminase 2 undergoes a large conformational change upon activation. PLoS Biol. 2007 Dec;5(12):e327.
  • Pardin C, Roy I, Lubell WD, et al. Reversible and competitive cinnamoyl triazole inhibitors of tissue transglutaminase. Chem Biol Drug Des. 2008 Sep;72(3):189–196.
  • Colak G, Keillor JW, Johnson GV. Cytosolic guanine nucledotide binding deficient form of transglutaminase 2 (R580a) potentiates cell death in oxygen glucose deprivation. PloS One. 2011 Jan 31;6(1):e16665.
  • Caron NS, Munsie LN, Keillor JW, et al. Using FLIM-FRET to measure conformational changes of transglutaminase type 2 in live cells. PloS One. 2012;7(8):e44159.
  • Keillor JW, Chica RA, Chabot N, et al. The bioorganic chemistry of transglutaminase - from mechanism to inhibition and engineering. Can J Chem. 2008 Apr;86(4):271–276.
  • Kerr C, Szmacinski H, Fisher ML, et al. Transamidase site-targeted agents alter the conformation of the transglutaminase cancer stem cell survival protein to reduce GTP binding activity and cancer stem cell survival. Oncogene. 2017 May 25;36(21):2981–2990.
  • Badarau E, Collighan RJ, Griffin M. Recent advances in the development of tissue transglutaminase (TG2) inhibitors. Amino Acids. 2013 Jan;44(1):119–127.
  • Keillor JW, Apperley KY. Transglutaminase inhibitors: a patent review. Expert Opin Ther Pat. 2016;26(1):49–63.
  • Keillor JW, Apperley KY, Akbar A. Inhibitors of tissue transglutaminase. Trends Pharmacol Sci. 2015 Jan;36(1):32–40.
  • Keillor JW, Chabot N, Roy I, et al. Irreversible inhibitors of tissue transglutaminase. Adv Enzymol Relat Areas Mol Biol. 2011;78:415–447.
  • Song M, Hwang H, Im CY, et al. Recent Progress in the Development of Transglutaminase 2 (TGase2) Inhibitors. J Med Chem. 2017 Jan 26;60(2):554–567.
  • Choi K, Siegel M, Piper JL, et al. Chemistry and biology of dihydroisoxazole derivatives: selective inhibitors of human transglutaminase 2. Chem Biol. 2005 Apr;12(4):469–475.
  • Watts RE, Siegel M, Khosla C. Structure-activity relationship analysis of the selective inhibition of transglutaminase 2 by dihydroisoxazoles. J Med Chem. 2006 Dec 14;49(25):7493–7501.
  • de Macedo P, Marrano C, Keillor JW. Synthesis of dipeptide-bound epoxides and alpha,beta-unsaturated amides as potential irreversible transglutaminase inhibitors. Bioorg Med Chem. 2002 Feb;10(2):355–360.
  • Marrano C, de Macedo P, Gagnon P, et al. Synthesis and evaluation of novel dipeptide-bound 1,2,4-thiadiazoles as irreversible inhibitors of Guinea pig liver transglutaminase. Bioorg Med Chem. 2001 Dec;9(12):3231–3241.
  • Akbar A, McNeil NMR, Albert MR, et al. Structure-activity relationships of potent, targeted covalent inhibitors that abolish both the transamidation and GTP binding activities of human tissue transglutaminase. J Med Chem. 2017 Sep 28;60(18):7910–7927.
  • Wityak J, Prime ME, Brookfield FA, et al. SAR development of lysine-based irreversible inhibitors of Transglutaminase 2 for Huntington’s disease. ACS Med Chem Lett. 2012 Dec 13;3(12):1024–1028.
  • Wodtke R, Hauser C, Ruiz-Gomez G, et al. N(epsilon)-Acryloyllysine Piperazides as irreversible inhibitors of Transglutaminase 2: synthesis, structure-activity relationships, and pharmacokinetic profiling. J Med Chem. 2018 May 24;61(10):4528–4560.
  • Wodtke R, Wodtke J, Hauser S, et al. Development of an (18) F-LabeledIrreversible inhibitor of Transglutaminase 2 as radiometric tool for quantitative expression profiling in cells and tissues. J Med Chem. 2021 Mar 25;64(6):3462–3478.
  • Hausch F, Halttunen T, Maki M, et al. Design, synthesis, and evaluation of gluten peptide analogs as selective inhibitors of human tissue transglutaminase. Chem Biol. 2003 Mar;10(3):225–231.
  • Schuppan D, Maki M, Lundin KEA, et al. A randomized trial of a Transglutaminase 2 inhibitor for Celiac disease. N Engl J Med. 2021 Jul 1;385(1):35–45.
  • Prime ME, Andersen OA, Barker JJ, et al. Discovery and structure-activity relationship of potent and selective covalent inhibitors of transglutaminase 2 for Huntington’s disease. J Med Chem. 2012 Feb 9;55(3):1021–1046.
  • Prime ME, Brookfield FA, Courtney SM, et al. Irreversible 4-Aminopiperidine Transglutaminase 2 inhibitors for Huntington’s disease. ACS Med Chem Lett. 2012 Sep 13;3(9):731–735.
  • Chrobok NL, Bol J, Jongenelen CA, et al. Characterization of Transglutaminase 2 activity inhibitors in monocytes in vitro and their effect in a mouse model for multiple sclerosis. PloS One. 2018;13(4):e0196433.
  • Badarau E, Wang Z, Rathbone DL, et al. Development of potent and selective tissue Transglutaminase Inhibitors: their effect on TG2 function and application in pathological conditions. Chem Biol. 2015 Oct 22;22(10):1347–1361.
  • Fell S, Wang Z, Blanchard A, et al. Transglutaminase 2: a novel therapeutic target for idiopathic pulmonary fibrosis using selective small molecule inhibitors. Amino Acids. 2021 Feb;53(2):205–217.
  • Kahlem P, Terre C, Green H, et al. 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. 1996 Dec 10;93(25):14580–14585.
  • Miller ML, Johnson GV. Transglutaminase cross-linking of the tau protein. J Neurochem. 1995 Oct;65(4):1760–1770.
  • Gundemir S, Colak G, Feola J, et al. Transglutaminase 2 facilitates or ameliorates HIF signaling and ischemic cell death depending on its conformation and localization. Biochim Biophys Acta. 2013 Jan;1833(1):1–10.
  • Gundemir S, Johnson GV. Intracellular localization and conformational state of transglutaminase 2: implications for cell death. PloS One. 2009 Jul 1;4(7):e6123.
  • Katt WP, Antonyak MA, Cerione RA. Opening up about tissue Transglutaminase: when conformation matters more than enzymatic activity. Med One. 2018;3:6.
  • Singh G, Zhang J, Ma Y, et al. The different conformational states of tissue transglutaminase have opposing affects on cell viability. J Biol Chem. 2016 Apr 22;291(17):9119–9132.
  • Selkoe DJ, Abraham C, Ihara Y. Brain transglutaminase: in vitro crosslinking of human neurofilament proteins into insoluble polymers. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6070–6074.
  • Zemaitaitis MO, Kim SY, Halverson RA, et al. Transglutaminase activity, protein, and mRNA expression are increased in progressive supranuclear palsy. J Neuropathol Exp Neurol. 2003 Feb;62(2):173–184.
  • Ebashi M, Ito Y, Uematsu M, et al. How to demix Alzheimer-type and PSP-type tau lesions out of their mixture -hybrid approach to dissect comorbidity. Acta Neuropathol Commun. 2019 May 6;7(1):71.
  • Shoeibi A, Olfati N, Litvan I. Frontrunner in translation: progressive supranuclear palsy. Front Neurol. 2019;10:1125.
  • Nemes Z, Devreese B, Steinert PM, et al. Cross-linking of ubiquitin, HSP27, parkin, and alpha-synuclein by gamma-glutamyl-epsilon-lysine bonds in Alzheimer’s neurofibrillary tangles. FASEB J. 2004 Jul;18(10):1135–1137.
  • Singer SM, Zainelli GM, Norlund MA, et al. Transglutaminase bonds in neurofibrillary tangles and paired helical filament tau early in Alzheimer’s disease. Neurochem Int. 2002 Jan;40(1):17–30.
  • Johnson GV, LeShoure R Jr. Immunoblot analysis reveals that isopeptide antibodies do not specifically recognize the epsilon-(gamma-glutamyl)lysine bonds formed by transglutaminase activity. J Neurosci Methods. 2004 Apr 30;134(2):151–158.
  • Wilhelmus MM, de Jager M, Smit AB, et al. Catalytically active tissue transglutaminase colocalises with Abeta pathology in Alzheimer’s disease mouse models. Sci Rep. 2016 Feb;3(6):20569.
  • Tai HC, Serrano-Pozo A, Hashimoto T, et al. The synaptic accumulation of hyperphosphorylated tau oligomers in Alzheimer disease is associated with dysfunction of the ubiquitin-proteasome system. Am J Pathol. 2012 Oct;181(4):1426–1435.
  • Ward SM, Himmelstein DS, Lancia JK, et al. Tau oligomers and tau toxicity in neurodegenerative disease. Biochem Soc Trans. 2012 Aug;40(4):667–671.
  • Zempel H, Luedtke J, Kumar Y, et al. Amyloid-beta oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin. EMBO J. 2013 Nov 13;32(22):2920–2937.
  • Lee HJ, Jung YH, Choi GE, et al. Urolithin A suppresses high glucose-induced neuronal amyloidogenesis by modulating TGM2-dependent ER-mitochondria contacts and calcium homeostasis. Cell Death Differ. 2021 Jan;28(1):184–202.
  • McConoughey SJ, Basso M, Niatsetskaya ZV, et al. Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington disease. EMBO Mol Med. 2010 Sep;2(9):349–370.
  • Citron BA, Suo Z, SantaCruz K, et al. Protein crosslinking, tissue transglutaminase, alternative splicing and neurodegeneration. Neurochem Int. 2002 Jan;40(1):69–78.
  • Vermes I, Steur EN, Jirikowski GF, et al. Elevated concentration of cerebrospinal fluid tissue transglutaminase in Parkinson’s disease indicating apoptosis. Mov Disord. 2004 Oct;19(10):1252–1254.
  • Grosso H, Woo JM, Lee KW, et al. Transglutaminase 2 exacerbates alpha-synuclein toxicity in mice and yeast. FASEB J. 2014 Oct;28(10):4280–4291.
  • Zhang J, Grosso Jasutkar H, Yan R, et al. Transglutaminase 2 depletion attenuates alpha-synuclein mediated toxicity in Mice. Neuroscience. 2020 Aug 10;441:58–64.
  • Segers-Nolten IM, Wilhelmus MM, Veldhuis G, et al. Tissue transglutaminase modulates alpha-synuclein oligomerization. Protein Sci. 2008 Aug;17(8):1395–1402.
  • A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. The Huntington’s Disease Collaborative Research Group. Cell. 1993 Mar 26;72(6):971–983.
  • Green H. Human genetic diseases due to codon reiteration: relationship to an evolutionary mechanism. Cell. 1993 Sep 24;74(6):955–956.
  • DiFiglia M, Sapp E, Chase KO, et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science. 1997 Sep 26;277(5334):1990–1993.
  • Kahlem P, Green H, Djian P. Transglutaminase action imitates Huntington’s disease: selective polymerization of Huntingtin containing expanded polyglutamine. Mol Cell. 1998 Mar;1(4):595–601.
  • Chun W, Lesort M, Tucholski J, et al. Tissue transglutaminase does not contribute to the formation of mutant huntingtin aggregates. J Cell Biol. 2001 Apr 2;153(1):25–34.
  • Konno T, Morii T, Hirata A, et al. Covalent blocking of fibril formation and aggregation of intracellular amyloidgenic proteins by transglutaminase-catalyzed intramolecular cross-linking. Biochemistry. 2005 Feb 15;44(6):2072–2079.
  • Konno T, Morii T, Shimizu H, et al. Paradoxical inhibition of protein aggregation and precipitation by transglutaminase-catalyzed intermolecular cross-linking. J Biol Chem. 2005 Apr 29;280(17):17520–17525.
  • Bailey CD, Johnson GV. Tissue transglutaminase contributes to disease progression in the R6/2 Huntington’s disease mouse model via aggregate-independent mechanisms. J Neurochem. 2005 Jan;92(1):83–92.
  • Mastroberardino PG, Iannicola C, Nardacci R, et al. ‘Tissue’ transglutaminase ablation reduces neuronal death and prolongs survival in a mouse model of Huntington’s disease. Cell Death Differ. 2002 9;Sep(9):873–880.
  • Menalled LB, Kudwa AE, Oakeshott S, et al. 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. 2014;9(6):e99520.
  • Lin Y, He H, Luo Y, et al. Inhibition of transglutaminase exacerbates polyglutamine-induced neurotoxicity by increasing the aggregation of mutant ataxin-3 in an SCA3 Drosophila model. Neurotox Res. 2015 Apr;27(3):259–267.
  • Schaertl S, Prime M, Wityak J, et al. A profiling platform for the characterization of transglutaminase 2 (TG2) inhibitors. J Biomol Screen. 2010 Jun;15(5):478–487.
  • Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017. 3. Mar(7):42717.
  • Daina A, Zoete V. A boiled-egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem. 2016 Jun 6;11(11):1117–1121.
  • Jeitner TM, Pinto JT, Cooper AJL. Cystamine and cysteamine as inhibitors of transglutaminase activity in vivo. Biosci Rep. 2018 Oct 31;38(5).
  • Palanski BA, Cystamine KC. Disulfiram inhibit human Transglutaminase 2 via an oxidative mechanism. Biochemistry. 2018 Jun 19;57(24):3359–3363.
  • Lesort M, Lee M, Tucholski J, et al. Cystamine inhibits caspase activity. Implications for the treatment of polyglutamine disorders. J Biol Chem. 2003 Feb 7;278(6):3825–3830.
  • Mao Z, Choo YS, Lesort M. Cystamine and cysteamine prevent 3-NP-induced mitochondrial depolarization of Huntington’s disease knock-in striatal cells. Eur J Neurosci. 2006 Apr;23(7):1701–1710.
  • Bailey CD, Johnson GV. The protective effects of cystamine in the R6/2 Huntington’s disease mouse involve mechanisms other than the inhibition of tissue transglutaminase. Neurobiol Aging. 2006 Jun;27(6):871–879.
  • Dedeoglu A, Kubilus JK, Jeitner TM, et al. Therapeutic effects of cystamine in a murine model of Huntington’s disease. J Neurosci. 2002 Oct 15;22(20):8942–8950.
  • Karpuj MV, Becher MW, Springer JE, et al. Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine. Nat Med. 2002 Feb;8(2):143–149.
  • Van Raamsdonk JM, Pearson J, Cd B, et al. Cystamine treatment is neuroprotective in the YAC128 mouse model of Huntington disease. J Neurochem. 2005 Oct;95(1):210–220.
  • Arbez N, Roby E, Akimov S, et al. Cysteamine protects neurons from mutant Huntingtin toxicity. J Huntingtons Dis. 2019;8(2):129–143.
  • Verny C, Bachoud-Levi AC, Durr A, et al. A randomized, double-blind, placebo-controlled trial evaluating cysteamine in Huntington’s disease. Mov Disord. 2017 Jun;32(6):932–936.
  • van Strien ME, Breve JJ, Fratantoni S, et al. Astrocyte-derived tissue transglutaminase interacts with fibronectin: a role in astrocyte adhesion and migration? PloS One. 2011;6(9):e25037.
  • Chrobok NL, Bol J, Wilhelmus MMM, et al. Tissue Transglutaminase appears in monocytes and macrophages but not in lymphocytes in white matter multiple sclerosis lesions. J Neuropathol Exp Neurol. 2019 Jun 1;78(6):492–500.
  • Yuan L, Siegel M, Choi K, et al. Transglutaminase 2 inhibitor, KCC009, disrupts fibronectin assembly in the extracellular matrix and sensitizes orthotopic glioblastomas to chemotherapy. Oncogene. 2007 Apr 19;26(18):2563–2573.
  • Katt WP, Antonyak MA, Cerione RA. The diamond anniversary of tissue transglutaminase: a protein of many talents. Drug Discov Today. 2018 Mar;23(3):575–591.
  • Espitia Pinzon N, van Mierlo H, de Jonge JC, et al. Tissue transglutaminase promotes early differentiation of oligodendrocyte progenitor cells. Front Cell Neurosci. 2019;13:281.
  • Sestito C, Breve JJP, Bol J, et al. Tissue Transglutaminase contributes to myelin phagocytosis in interleukin-4-treated human monocyte-derived macrophages. Cytokine. 2020;128:155024.
  • Sestito C, Leurs CE, and Steenwijk MD, et al. Tissue Transglutaminase expression associates with progression of multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2021 Jul;8(4).
  • Ientile R, Caccamo D, Marciano MC, et al. Transglutaminase activity and transglutaminase mRNA transcripts in gerbil brain ischemia. Neurosci Lett. 2004 Jun 10;363(2):173–177.
  • Feola J, Barton A, Akbar A, et al. Transglutaminase 2 modulation of NF-kappaB signaling in astrocytes is independent of its ability to mediate astrocytic viability in ischemic injury. Brain Res. 2017 Aug 1;1668:1–11.
  • Shi W, Que Y, Lv D, et al. Overexpression of TG2 enhances the differentiation of ectomesenchymal stem cells into neuronlike cells and promotes functional recovery in adult rats following spinal cord injury. Mol Med Rep. 2019 Sep;20(3):2763–2773.
  • Yunes-Medina L, Paciorkowski A, Nuzbrokh Y, et al. Depletion of transglutaminase 2 in neurons alters expression of extracellular matrix and signal transduction genes and compromises cell viability. Mol Cell Neurosci. 2018;86:72–80.
  • Gundemir S, Monteagudo A, Akbar A, et al. The complex role of transglutaminase 2 in glioblastoma proliferation. Neuro Oncol. 2017 Sep 2;19:208–218.
  • Elahi A, Emerson J, Rudlong J, et al. Deletion or inhibition of astrocytic transglutaminase 2 promotes functional recovery after spinal cord injury. BIORXIV-2021-460455v1. 2021:under review.
  • Baillie TA. Targeted Covalent Inhibitors for Drug Design. Angew Chem Int Ed Engl. 2016 Oct 17;55(43):13408–13421.
  • Klock C, Herrera Z, Albertelli M, et al. Discovery of potent and specific dihydroisoxazole inhibitors of human transglutaminase 2. J Med Chem. 2014 Nov 13;57(21):9042–9064.
  • McEwen DP, Gee KR, Kang HC, et al. Fluorescent BODIPY-GTP analogs: real-time measurement of nucleotide binding to G proteins. Anal Biochem. 2001 Apr 1;291(1):109–117.
  • Jang TH, Lee DS, Choi K, et al. Crystal structure of transglutaminase 2 with GTP complex and amino acid sequence evidence of evolution of GTP binding site. PloS One. 2014;9(9):e107005.
  • Arrasate M, Finkbeiner S. Protein aggregates in Huntington’s disease. Exp Neurol. 2012 Nov;238(1):1–11.
  • Benilova I, Karran E, De Strooper B. The toxic Abeta oligomer and Alzheimer’s disease: an emperor in need of clothes. Nat Neurosci. 2012 Jan 29;15(3):349–357.
  • Winner B, Jappelli R, Maji SK, et al. In vivo demonstration that alpha-synuclein oligomers are toxic. Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4194–4199.

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