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Review
. 2015 Jun 15:8:21.
doi: 10.3389/fnmol.2015.00021. eCollection 2015.

The role of the ubiquitin-editing enzyme A20 in diseases of the central nervous system and other pathological processes

Asghar Abbasi  1 , Kirsi Forsberg  1 , Felix Bischof  1
Affiliations
Review

The role of the ubiquitin-editing enzyme A20 in diseases of the central nervous system and other pathological processes

Asghar Abbasi et al. Front Mol Neurosci. .

Abstract

In recent years, the ubiquitin-editing enzyme A20 has been shown to control a large set of molecular pathways involved in the regulation of protective as well as self-directed immune responses. Here, we assess the current and putative roles of A20 in inflammatory, vascular and degenerative diseases of the central nervous system and explore future directions of research.

Keywords: A20; NF-κB; central nervous system; neurodegenerative diseases; neuroinflammation.

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Figures

Figure 1
Figure 1
Domain structure of A20. OTU ubiquitin protease domain and zinc fingers domains are depicted in blue and yellow boxes, respectively. Picture adopted from Enesa and Evans (2014).
Figure 2
Figure 2
The pathologic role of TCR, BCR and TH17-induced MALT-1 in demyelination and the inhibition of this signaling pathway by A20. As depicted in Figure 2, downstream of CBM, IKK complex is activated by MALT-1 that in turn, plays an essential role in the development of EAE-mediated Demyelination. MALT1, in other hand, cleaves the NF-κB inhibitory proteins A20 and CYLD as well as the NF-κB subunit RelB in antigen receptor-stimulated T cells and during EAE, suggesting a contribution of MALT1 proteolytic activity in T cell activation and EAE development. A20, negatively regulates TCR and BCR signaling to NF-κB by cleaving MALT-1 ubiquitin chains and therefore contributes to balance TCR/BCR-induced IKK/NF-KB signaling. Activated A20 might play an important role in protecting neural cells against autoimmune mediated demyelination.
Figure 3
Figure 3
The essential role of A20 in the regulation of NF-κB in neurons, astrocytes and microglia. Several factors including inflammation, brain injury and stroke and toxins can induce the production and activation of NF-κB transcription factor in various cells of CNS. Activation of NF-κB, results in the induction of several inflammatory mediators as well as the activation of Ubiquitin-editing enzyme A20. A20, in turn, negatively regulates NF-κB signaling and preserves CNS-specific homeostasis.
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