Abstract
Inflammation is a highly regulated process involved both in the response to pathogens as well as in tissue homeostasis. In recent years, a complex network of proteins in charge of inflammation control has been revealed by the study of hereditary periodic fever syndromes. Most of these proteins belong to a few families and share the capability of sensing pathogen-associated and damageassociated molecular patterns. By interacting with each other, these proteins participate in the assembly of molecular platforms, called inflammasomes, which ultimately lead to the activation of cytokines, to the transcription of inflammatory genes or to the induction of cell apoptosis. Among hereditary periodic fever syndromes, mevalonate kinase deficiency (MKD) is the sole in which the phenotype did not directly associate with a deficiency of these proteins, but with a metabolic defect of the mevalonate pathway, highlighting the importance of this metabolic pathway in the inflammation control. Noteworthy, drugs acting on this pathway can greatly influence the inflammatory response. The modulation of inflammation by mevalonate pathway is of interest, since it may involve mechanisms not directly referable to inflammasomes. MKD provides a model to study these mechanisms and possibly to develop new classes of anti-inflammatory drugs.
Keywords: Mevalonate, statin, aminobisphosphonate, inflammation, cholesterol
Current Pharmaceutical Design
Title:Mevalonate Kinase Deficiency: Disclosing the Role of Mevalonate Pathway Modulation in Inflammation
Volume: 18 Issue: 35
Author(s): Annalisa Marcuzzi, Sergio Crovella, Lorenzo Monasta, Liza Vecchi Brumatti, Marco Gattorno and Joost Frenkel
Affiliation:
Keywords: Mevalonate, statin, aminobisphosphonate, inflammation, cholesterol
Abstract: Inflammation is a highly regulated process involved both in the response to pathogens as well as in tissue homeostasis. In recent years, a complex network of proteins in charge of inflammation control has been revealed by the study of hereditary periodic fever syndromes. Most of these proteins belong to a few families and share the capability of sensing pathogen-associated and damageassociated molecular patterns. By interacting with each other, these proteins participate in the assembly of molecular platforms, called inflammasomes, which ultimately lead to the activation of cytokines, to the transcription of inflammatory genes or to the induction of cell apoptosis. Among hereditary periodic fever syndromes, mevalonate kinase deficiency (MKD) is the sole in which the phenotype did not directly associate with a deficiency of these proteins, but with a metabolic defect of the mevalonate pathway, highlighting the importance of this metabolic pathway in the inflammation control. Noteworthy, drugs acting on this pathway can greatly influence the inflammatory response. The modulation of inflammation by mevalonate pathway is of interest, since it may involve mechanisms not directly referable to inflammasomes. MKD provides a model to study these mechanisms and possibly to develop new classes of anti-inflammatory drugs.
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Cite this article as:
Marcuzzi Annalisa, Crovella Sergio, Monasta Lorenzo, Vecchi Brumatti Liza, Gattorno Marco and Frenkel Joost, Mevalonate Kinase Deficiency: Disclosing the Role of Mevalonate Pathway Modulation in Inflammation, Current Pharmaceutical Design 2012; 18 (35) . https://dx.doi.org/10.2174/138161212803530835
DOI https://dx.doi.org/10.2174/138161212803530835 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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