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A Disintegrin and Metalloproteinase-Control Elements in Infectious Diseases.
Ahmad Aljohmani1, Daniela Yildiz1
1Institute of Experimental and Clinical Pharmacology and Toxicology, PZMS, ZHMB, Saarland University, Homburg, Germany.
Frontiers in Cardiovascular Medicine
|January 4, 2021
Summary
A disintegrin and metalloproteinase (ADAM) proteases and their substrate shedding play key roles in infectious diseases. Dysregulation of ADAMs contributes to chronic inflammation and systemic tissue damage, including cardiovascular issues.
Area of Science:
- Immunology
- Molecular Biology
- Pathophysiology
Background:
- Infectious diseases remain a leading global cause of death, with persistent inflammation leading to tissue damage.
- The immune system's initial response involves pattern-recognition receptors and cytokine release.
- Members of the 'a disintegrin and metalloproteinase' (ADAM) family are involved in ectodomain shedding of transmembrane proteins.
Purpose of the Study:
- To review the function of ADAM proteases and regulated intramembrane proteolysis (RIPing) in infectious diseases.
- To explore the role of ADAM substrates in pathogen recognition and clearance.
- To discuss the long-term pathophysiological consequences of ADAM dysregulation in infectious diseases, particularly cardiovascular changes.
Main Methods:
- Literature review summarizing current knowledge on ADAM function in infection.
- Analysis of ADAM substrate dysregulation in infectious disease contexts.
- Discussion of RIPing pathways influenced by ADAMs.
Main Results:
- Dysregulation of ADAM substrates, including junction and adhesion molecules, and cytokines, is observed in infectious diseases.
- ADAM-mediated alpha-cleavage is a rate-limiting step for RIPing, impacting cellular processes.
- ADAM substrates and RIPing contribute to systemic damage in cardiovascular, endocrine, and gastrointestinal systems.
Conclusions:
- ADAM proteases and RIPing are critical in the immune response to pathogens.
- Dysfunctional ADAM activity in infectious diseases can lead to chronic inflammation and significant tissue damage.
- Understanding ADAMs' role is crucial for addressing long-term complications like cardiovascular diseases.
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