title: HMGB1 as biomarker and drug target.
abstract: High Mobility Group Box 1 protein was discovered as a nuclear protein, but it has a "second life" outside the cell where it acts as a damage-associated molecular pattern. HMGB1 is passively released or actively secreted in a number of diseases, including trauma, chronic inflammatory disorders, autoimmune diseases and cancer. Extracellular HMGB1 triggers and sustains the inflammatory response by inducing cytokine release and by recruiting leucocytes. These characteristics make extracellular HMGB1 a key molecular target in multiple diseases. A number of strategies have been used to prevent HMGB1 release or to inhibit its activities. Current pharmacological strategies include antibodies, peptides, decoy receptors and small molecules. Noteworthy, salicylic acid, a metabolite of aspirin, has been recently found to inhibit HMGB1. HMGB1 undergoes extensive post-translational modifications, in particular acetylation and oxidation, which modulate its functions. Notably, high levels of serum HMGB1, in particular of the hyper-acetylated and disulfide isoforms, are sensitive disease biomarkers and are associated with different disease stages. In the future, the development of isoform-specific HMGB1 inhibitors may potentiate and fine-tune the pharmacological control of inflammation. We review here the current therapeutic strategies targeting HMGB1, in particular the emerging and relatively unexplored small molecules-based approach.
authors.affiliation: Chromatin Dynamics Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; HMGBiotech s.r.l., Milan, Italy.
authors.forename: Emilie
authors.initials: E
authors.lastname: Venereau
authors.affiliation: Biomolecular NMR Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: De Leo
authors.affiliation: Chromatin Dynamics Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Mezzapelle
authors.affiliation: Chromatin Dynamics Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; University of Milano Bicocca, Milan, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Careccia
authors.affiliation: Biomolecular NMR Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Musco
authors.affiliation: Chromatin Dynamics Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; San Raffaele University, Milan, Italy. Electronic address: bianchi.marco@hsr.it.
authors.forename: Marco E
authors.initials: ME
authors.lastname: Bianchi
mesh_terms: D000818:Animals; D001688:Biological Products / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy
chemical_list: D001688:Biological Products; D015415:Biomarkers; D024243:HMGB1 Protein
keywords: Autoimmunity; Cancer; Inflammation; Redox; Sepsis; Trauma