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. 2021 Dec 7;9(12):1857. doi: 10.3390/biomedicines9121857

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Thalidomide as alternative therapy in CLE. (a) Thalidomide binds CRBN in the cullin-4 E3 ubiquitin ligase complex (CRL4^CRBN) and promotes: A downregulation of mTOR protein, by reducing the AMPK ubiquitination and increasing the RPTOR phosphorylation that downregulated NF-ҡB and its related cytokines in keratinocytes. Also promoted is a reduction of IRF4 expression in lymphocytes that decreases the expression of NF-ҡB and related cytokines. In addition, thalidomide enhances tissue reparation promoting Th2 responses, iNK T cells and lower prevalence of CD8+ T cells. (b) Alternative therapeutic drugs targeting NF-ҡB signalling may avoid its important side effects and maintain its anti-inflammatory properties.