Notch Signaling Regulation in Autoinflammatory Diseases

• Published in: International journal of molecular sciences 2020-11, Vol.21 (22), p.8847
• Main Authors: Gratton, Rossella, Tricarico, Paola Maura, d'Adamo, Adamo Pio, Bianco, Anna Monica, Moura, Ronald, Agrelli, Almerinda, Brandão, Lucas, Zupin, Luisa, Crovella, Sergio
• Format: Article
• Language: English
• Subjects: Animals; Arteritis; Behcet Syndrome - genetics; Behcet Syndrome - pathology; Behcet's syndrome; Cell death; Cell differentiation; Cell Differentiation - genetics; Cell fate; Crosstalk; Cytokines; Disease; Genes; Giant Cell Arteritis - genetics; Giant Cell Arteritis - pathology; Hereditary Autoinflammatory Diseases - classification; Hereditary Autoinflammatory Diseases - genetics; Hereditary Autoinflammatory Diseases - pathology; Hidradenitis Suppurativa - genetics; Hidradenitis Suppurativa - pathology; Humans; Immune system; Inflammation; Inflammation - genetics; Inflammation - pathology; Inflammatory diseases; Intracellular signalling; Ligands; Molecular modelling; Mutation; Mutation - genetics; Receptors, Notch - genetics; Review; Signal transduction; Signal Transduction - genetics; Transcription factors; Tumor necrosis factor-TNF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21228847

Notch pathway is a highly conserved intracellular signaling route that modulates a vast variety of cellular processes including proliferation, differentiation, migration, cell fate and death. Recently, the presence of a strict crosstalk between Notch signaling and inflammation has been described, although the precise molecular mechanisms underlying this interplay have not yet been fully unravelled. Disruptions in Notch cascade, due both to direct mutations and/or to an altered regulation in the core components of Notch signaling, might lead to hypo- or hyperactivation of Notch target genes and signaling molecules, ultimately contributing to the onset of autoinflammatory diseases. To date, alterations in Notch signaling have been reported as associated with three autoinflammatory disorders, therefore, suggesting a possible role of Notch in the pathogenesis of the following diseases: hidradenitis suppurativa (HS), Behçet disease (BD), and giant cell arteritis (GCA). In this review, we aim at better characterizing the interplay between Notch and autoinflammatory diseases, trying to identify the role of this signaling route in the context of these disorders.