Amino Acids

, Volume 47, Issue 1, pp 19–26 | Cite as

Transglutaminase 2 and neuroinflammation

Invited Review

Abstract

Neuroinflammatory processes seem to play a pivotal role in various chronic neurodegenerative diseases, characterized also by the pathogenetic accumulation of specific protein aggregates. Several of these proteins have been shown to be substrates of transglutaminases, calcium-dependent enzymes that catalyze protein crosslinking reactions. However, it has recently been demonstrated that transglutaminase 2 (TG2) may also be involved in molecular mechanisms underlying inflammation. In the central nervous system, astrocytes and microglia are the cell types mainly involved in the inflammatory process. This review is focused on the increases of TG2 protein expression and enzyme activity that occur in astroglial, microglial and monocyte cell models in response to inflammatory stimuli. The transcription factor NF-κB is considered the main regulator of inflammation, being activated by a variety of stimuli including calcium influx, oxidative stress and inflammatory cytokines. Under these conditions, the over-expression of TG2 results in the sustained activation of NF-κB. Several findings emphasize the possible role of the TG2/NF-κB activation pathway in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and amyotrophic lateral sclerosis. Although further studies are needed to characterize the TG2/NF-κB cross-talk in monocytes/macrophages/microglia within the central nervous system, some results show that TG2 and NF-κB are co-localized in cell compartments. Together, evidence suggests that TG2 plays a role in neuroinflammation and contributes to the production of compounds that are potentially deleterious to neuronal cells.

Keywords

Transglutaminase 2 Neuroinflammation Microglia NF-κB 

Abbreviations

Amyloid β

AD

Alzheimer’s disease

ALS

Amyotrophic lateral sclerosis

CSF

Cerebrospinal fluid

DA

Dopaminergic

HD

Huntington disease

Hsps

Heat shock proteins

Htt

Huntingtin

IL-1β

Interleukin-1β

IL-6

Interleukin-6

IL-8

Interleukin-8

LPS

Lipopolysaccharide

MS

Multiple sclerosis

NF-κB

Nuclear factor-kappa B

NO

Nitric oxide

PD

Parkinson’s disease

PLA2

Phospholipase A2

SOD1

Superoxide dismutase 1

TG2

Tissue transglutaminase

TG2-S

TG2 short form

TGM2

Transglutaminase 2 gene

TGs

Transglutaminases

TNF-α

Tumor necrosis factor-α

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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Riccardo Ientile
    • 1
  • Monica Currò
    • 1
  • Daniela Caccamo
    • 1
  1. 1.Department of Biomedical Sciences and Morphological and Functional ImagingUniversity of MessinaMessinaItaly

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