Citation: Costa, D.; Scalise, E.; Ielapi, N.; Bracale, U.M.; Andreucci, M.; Serra, R. Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease. Biomolecules 2024, 14, 96. https:// doi.org/10.3390/biom14010096 Academic Editor: Andrey A. Zamyatnin, Jr. Received: 11 December 2023 Revised: 5 January 2024 Accepted: 10 January 2024 Published: 11 January 2024 Copyright: © 2024 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/). biomolecules Review Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease Davide Costa 1,2,† , Enrica Scalise 1,2,† , Nicola Ielapi 3 , Umberto Marcello Bracale 4 , Michele Andreucci 5, * and Raffaele Serra 1,2, * 1 Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; davide.costa@unicz.it (D.C.); enrica.scalise@unicz.it (E.S.) 2 Interuniversity Center of Phlebolymphology (CIFL), Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy 3 Department of Public Health and Infectious Disease, “Sapienza” University of Rome, 00185 Rome, Italy; nicola.ielapi@uniroma1.it 4 Department of Public Health, University Federico II of Naples, 80131 Naples, Italy; umbertomarcello.bracale@unina.it 5 Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy * Correspondence: andreucci@unicz.it (M.A.); rserra@unicz.it (R.S.) † These authors contributed equally to this work. Abstract: Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of this review are to analyze a specific family of MPs, the matrix metalloproteinases (MMPs), in the most common chronic and complex diseases that affect patients’ social lives and to better understand the nature of the associations between MMPs and the psychosocial environment. In accordance with the PRISMA extension for a scoping review, an examination was carried out. A collection of 24 studies was analyzed, focusing on the molecular mechanisms of MMP and their connection to the manifestation of social aspects in human disease. The complexity of the relationship between MMP and social problems is presented via an interdisciplinary approach based on complexity paradigm as a new approach for conceptualizing knowledge in health research. Finally, two implications emerge from the study: first, the psychosocial states of individuals have a profound impact on their overall health and disease conditions, which implies the importance of adopting a holistic perspective on human well-being, encompassing both physical and psychosocial aspects. Second, the use of MPs as biomarkers may provide physicians with valuable tools for a better understanding of disease when used in conjunction with “sociomarkers” to develop mathematical predictive models. Keywords: matrix metalloproteinases; psychosocial aspects; complexity science; complexity paradigm; chronic diseases; health; well-being; interdisciplinary approach; biomarkers; sociomarkers 1. Introduction Proteases are important enzymes that are involved in many aspects of biology, and proteolysis plays a key role in protein post-translational modifications. The 473 human proteases are divided into five classes of catalysis as reported in the MEROPS database: metallo (148), serine (152), cysteine (136), aspartic acid (21), and threonine proteases. The main function of proteases is to cleave or degrade all proteins [1–4]. Metalloproteinases (MPs) are a group of multidomain zinc-dependent endopeptidases named metzincin pro- teases, which are divided into six families: astacins (an enzyme found in various bacterial species and humans), adamalysins or ADAMS (consisting of a disintegrin and metallopro- teinase), ADAMTS (consisting of a disintegrin and metalloproteinase with thrombospondin motif), pappalysin (pregnancy-associated plasma protein), serralysin (bacterial enzyme), and matrix metalloproteinases (MMP) or matrixin [4–7]. The name “metzincins” originates Biomolecules 2024, 14, 96. https://doi.org/10.3390/biom14010096 https://www.mdpi.com/journal/biomolecules