Temperature and Drug Treatments in Mevalonate Kinase Deficiency: An Ex Vivo Study
Joint Authors
Marcuzzi, Annalisa
Crovella, Sérgio
Tricarico, Paola Maura
Piscianz, Elisa
Zanin, Valentina
Kleiner, Giulio
Monasta, Lorenzo
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-08-29
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Mevalonate Kinase Deficiency (MKD) is a rare autosomal recessive inborn disorder of cholesterol biosynthesis caused by mutations in the mevalonate kinase (MK) gene, leading to MK enzyme decreased activity.
The consequent shortage of mevalonate-derived isoprenoid compounds results in an inflammatory phenotype, caused by the activation of the NALP3 inflammasome that determines an increased caspase-1 activation and IL-1β release.
In MKD, febrile temperature can further decrease the residual MK activity, leading to mevalonate pathway modulation and to possible disease worsening.
We previously demonstrated that the administration of exogenous isoprenoids such as geraniol or the modulation of the enzymatic pathway with drugs, such as Tipifarnib, partially rescues the inflammatory phenotype associated with the defective mevalonic pathway.
However, it has not been investigated yet how temperature can affect the success of these treatments.
Thus, we investigated the effect of temperature on primary human monocytes from MKD patients.
Furthermore the ability of geraniol and Tipifarnib to reduce the abnormal inflammatory response, already described at physiological temperature in MKD, was studied in a febrile condition.
We evidenced the role of temperature in the modulation of the inflammatory events and suggested strongly considering this variable in future researches aimed at finding a treatment for MKD.
American Psychological Association (APA)
Tricarico, Paola Maura& Kleiner, Giulio& Piscianz, Elisa& Zanin, Valentina& Monasta, Lorenzo& Crovella, Sérgio…[et al.]. 2013. Temperature and Drug Treatments in Mevalonate Kinase Deficiency: An Ex Vivo Study. BioMed Research International،Vol. 2013, no. 2013, pp.1-8.
https://search.emarefa.net/detail/BIM-1030830
Modern Language Association (MLA)
Tricarico, Paola Maura…[et al.]. Temperature and Drug Treatments in Mevalonate Kinase Deficiency: An Ex Vivo Study. BioMed Research International No. 2013 (2013), pp.1-8.
https://search.emarefa.net/detail/BIM-1030830
American Medical Association (AMA)
Tricarico, Paola Maura& Kleiner, Giulio& Piscianz, Elisa& Zanin, Valentina& Monasta, Lorenzo& Crovella, Sérgio…[et al.]. Temperature and Drug Treatments in Mevalonate Kinase Deficiency: An Ex Vivo Study. BioMed Research International. 2013. Vol. 2013, no. 2013, pp.1-8.
https://search.emarefa.net/detail/BIM-1030830
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1030830