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Transglutaminase

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

Transglutaminases (TGases) catalyze the Ca2+-dependent cross-linking of a glutaminyl (Q) residue in a protein or peptide substrate to a lysyl (K) residue in another protein or peptide substrate. These enzymes also catalyze the nucleophilic attack of amines, diamines, or polyamines on Q residues of protein or peptide substrates. TGases occur widely in nature. In rodents and humans, the TGase family is composed of nine members, eight of which are catalytically active. Human and mouse brain contain at least three TGase isoenzymes, namely TGase 1, TGase 2 (tTGase; so named because it is present in most mammalian tissues), and TGase 3. These enzymes have been implicated in some specialized neuronal functions, but generally their normal physiological roles in the central nervous system (CNS) are not well understood and have not been systematically studied. In contrast, the possible involvement of TGases in neurodegenerative diseases has been much more widely studied, especially within the last 5 years. As a result, this chapter contains more information on the roles of TGase in diseased brains than in healthy brains. Brain TGase activity and protein cross-linking are increased in several neurodegenerative diseases, including Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), and supranuclear palsy (SNP). Such increased activity may at first be protective by removing damaged and unfolded protein, but with time the process may become pathological and contribute to the downward spiral in neurodegenerative diseases. If this hypothesis is confirmed, specific TGase inhibitors may be of therapeutic benefit in these diseases.

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Abbreviations

AD:

Huntington disease

BDNF:

brain derived neurotrophic factor

CBP:

CRE binding protein

CNS:

central nervous system

CSF:

cerebrospinal fluid

CRE:

cAMP response element

DPLA:

dentatorubral-pallidoluysian atrophy

GGEL:

N ɛ-(γ-L-glutamyl)-L-lysine

HD:

Huntington disease

htt:

huntingtin

K:

lysine

PD:

Parkinson disease

PSP:

progressive supranuclear palsy

Q:

glutamine

Qn :

polyglutamine

NRSE:

neuronal restriction silencer element

SBMA:

spinobulbar muscular atrophy (Kennedy's disease)

SCA:

spinocerebellar ataxia

SNP:

supranuclear palsy

TBP:

TATA binding protein

TGase:

transglutaminase

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Acknowledgments

Work from our laboratory mentioned here was supported in part by NIH grant 1PO1AG14930.

Authors
  1. A. J. L. Cooper
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  2. S.-Y. Kim
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, Newyork, 10962, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosciences Division of Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street Suite 309, Charleston, SC 29425, USA

    Naren Banik (Professor) (Professor)

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Cooper, A.J.L., Kim, SY. (2007). Transglutaminase. In: Lajtha, A., Banik, N. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30379-6_7

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