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.