Multifaceted Role of Matrix Metalloproteases on Human Diseases
Matrix metalloproteases (MMPs) are important enzymes required in extracellular matrix (ECM) degradation for creating the cellular environments to maintain numerous physiological processes ranging from development to wound repair. However, MMP activity is
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Multifaceted Role of Matrix Metalloproteases on Human Diseases Soumitra Roy, Asmita Pramanik, Tapati Chakraborti and Sajal Chakraborti
Abstract
Matrix metalloproteases (MMPs) are important enzymes required in extracellular matrix (ECM) degradation for creating the cellular environments to maintain numerous physiological processes ranging from development to wound repair. However, MMP activity is strictly controlled and imbalance in the levels of MMP family members and its inhibitors has been implicated as an etiological factor in several diseases. Herein, involvement of MMPs and their natural inhibitors, tissue inhibitors of metalloproteases (TIMPs), in several disease processes have been considered for discussion. Keywords
MMP
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TIMP AD PD ALS
Introduction
Matrix metalloproteases (MMPs) are zinc-containing endopeptidases capable of degrading various components of extracellular matrix (ECM) [1]. They are produced as latent zymogens (pro-MMPs). Once activated, they participate in the regulation of
S. Roy (&) Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel e-mail: [email protected] A. Pramanik T. Chakraborti S. Chakraborti Department of Biochemistry and Biophysics, University of Kalyani, Kalyani 741235, West Bengal, India © Springer Nature Singapore Pte Ltd. 2017 S. Chakraborti et al. (eds.), Proteases in Human Diseases, DOI 10.1007/978-981-10-3162-5_2
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diverse physiological and pathological processes. Since its discovery about a few decades ago, MMPs have emerged as crucial mediators in defining interaction of cells with their surrounding microenvironment [2]. MMPs can be categorized into five major groups according to their substrate specificity: collagenases, gelatinases, membrane-type metalloproteases, stromelysins, and matrilysins [3]. MMP activity is tightly regulated at the transcriptional as well as at the post-translational level. MMPs enzymatic activities are controlled by tissue inhibitors of metalloproteases (TIMPs) after secretion in the extracellular milieu [4]. Among the four distinct TIMP molecules (TIMP-1, TIMP-2, TIMP-3, and TIMP-4), TIMP-1 is the major endogenous inhibitor of pro and active MMP-9 and inhibits their activity by forming a noncovalent complex [5]. The ECM is a three-dimensional, extracellular scaffold required for maintenance of life. Every tissue and organ is composed of ECM generated in early embryonic stages. The ECM provides structural support for organs, tissues, cell layers and for individual cells as substrates for cell motility. The function of ECM is much more than to provide physical support for tissues and organs; the ECM is constantly remodeled to provide a dynamic structure during tissue homeostasis [6]. MMPs can impact the development of several diseases through different pathophysiological mechanisms, mainly via tissue destruction and ECM degradation. Imbalance in MMP/TIMP ratio can cause a threat to mortality and severity of diseases. This
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