Matrix Metalloproteinases: From Structure to Function
A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Motility and Adhesion".
Deadline for manuscript submissions: closed (20 December 2021) | Viewed by 39618
Special Issue Editors
Interests: matrix metalloprotease-9; immunology; autoimmune diseases; inflammation; glycobiology; neutrophil biology; neuroinflammation
Interests: proteolysis; inflammation; MMPs; neutrophils; innate immune system; protease inhibition; alpha-2-macroglobulin
Special Issue Information
Dear Colleagues,
Matrix metalloproteases (MMPs) are a family of secreted or cell-bound zinc-dependent endopeptidases. While originally considered as matrix-remodelling enzymes (hence their name), many studies have revealed that MMPs have broader roles than matrix remodelling. Indeed, MMP substrates are found in the extracellular milieu associated with the cell membrane and even intracellularly. Not surprisingly, the impact of MMPs on life is broad, ranging from vital physiological processes to the initiation and progression of diseases. MMPs are essential for morphogenic and developmental processes including blood vessel remodelling and bone ossification. They are needed for normal tissue function and contribute to wound healing and repair, reproductive processes, and the innate immune defence. In contrast, the aberrant regulation of MMPs contributes to disease progression, for example, (auto-)inflammation (e.g., asthma and rheumatoid arthritis), neuropathology (e.g., multiple sclerosis), and cancer.
Although the significance of MMPs in homeostasis and disease is clear, fundamental information on MMP structures and in vivo functions remains limited. The importance of such information was illustrated several decades ago. Based on the finding of MMP up-regulation in malignant cancer tissue, it was suggested that MMPs are crucial to tumor growth and metastasis. Hence, several synthetic broad-spectrum MMP inhibitors were developed and evaluated in human clinical trials. Unfortunately, the outcomes were disappointing due to poor bioavailability and severe side-effects. Over the years, we have learned that MMPs work beyond classical connective tissue remodeling, that MMPs are tightly and differentially regulated, that different MMPs have different roles and different substrates, that MMPs are multi-domain enzymes with unique domain functions, and that MMPs have actions devoid of their proteolytic activity. Therefore, it is clear that only a detailed and critical (re-)analysis of MMP structures and functions will yield information and insights for their successful exploitation as disease targets.
The aim of this Special Issue is to explore and summarize the latest developments in MMP research with a focus on structural biological aspects and their functional implications. We invite experts to contribute high-quality original papers, research communications, or reviews.
Prof. Ghislain Opdenakker
Dr. Jennifer Vandooren
Dr. Estefania Ugarte-Berzal
Guest Editors
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Keywords
- matrix metalloproteases
- proteolysis
- immunology
- cancer
- extracellular matrix
- disease
- protease inhibition
- infection
- inhibitor
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