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Mevalonate Kinase Deficiency and Neuroinflammation: Balance between Apoptosis and Pyroptosis

Mevalonic aciduria, a rare autosomal recessive disease, represents the most severe form of the periodic fever, known as Mevalonate Kinase Deficiency. This disease is caused by the mutation of the MVK gene, which codes for the enzyme mevalonate kinase, along the cholesterol pathway. Mevalonic aciduri...

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Autores principales: Tricarico, Paola Maura, Marcuzzi, Annalisa, Piscianz, Elisa, Monasta, Lorenzo, Crovella, Sergio, Kleiner, Giulio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876043/
https://www.ncbi.nlm.nih.gov/pubmed/24287904
http://dx.doi.org/10.3390/ijms141223274
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author Tricarico, Paola Maura
Marcuzzi, Annalisa
Piscianz, Elisa
Monasta, Lorenzo
Crovella, Sergio
Kleiner, Giulio
author_facet Tricarico, Paola Maura
Marcuzzi, Annalisa
Piscianz, Elisa
Monasta, Lorenzo
Crovella, Sergio
Kleiner, Giulio
author_sort Tricarico, Paola Maura
collection PubMed
description Mevalonic aciduria, a rare autosomal recessive disease, represents the most severe form of the periodic fever, known as Mevalonate Kinase Deficiency. This disease is caused by the mutation of the MVK gene, which codes for the enzyme mevalonate kinase, along the cholesterol pathway. Mevalonic aciduria patients show recurrent fever episodes with associated inflammatory symptoms, severe neurologic impairments, or death, in early childhood. The typical neurodegeneration occurring in mevalonic aciduria is linked both to the intrinsic apoptosis pathway (caspase-3 and -9), which is triggered by mitochondrial damage, and to pyroptosis (caspase-1). These cell death mechanisms seem to be also related to the assembly of the inflammasome, which may, in turn, activate pro-inflammatory cytokines and chemokines. Thus, this particular molecular platform may play a crucial role in neuroinflammation mechanisms. Nowadays, a specific therapy is still lacking and the pathogenic mechanisms involving neuroinflammation and neuronal dysfunction have not yet been completely understood, making mevalonic aciduria an orphan drug disease. This review aims to analyze the relationship among neuroinflammation, mitochondrial damage, programmed cell death, and neurodegeneration. Targeting inflammation and degeneration in the central nervous system might help identify promising treatment approaches for mevalonic aciduria or other diseases in which these mechanisms are involved.
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spelling pubmed-38760432013-12-31 Mevalonate Kinase Deficiency and Neuroinflammation: Balance between Apoptosis and Pyroptosis Tricarico, Paola Maura Marcuzzi, Annalisa Piscianz, Elisa Monasta, Lorenzo Crovella, Sergio Kleiner, Giulio Int J Mol Sci Review Mevalonic aciduria, a rare autosomal recessive disease, represents the most severe form of the periodic fever, known as Mevalonate Kinase Deficiency. This disease is caused by the mutation of the MVK gene, which codes for the enzyme mevalonate kinase, along the cholesterol pathway. Mevalonic aciduria patients show recurrent fever episodes with associated inflammatory symptoms, severe neurologic impairments, or death, in early childhood. The typical neurodegeneration occurring in mevalonic aciduria is linked both to the intrinsic apoptosis pathway (caspase-3 and -9), which is triggered by mitochondrial damage, and to pyroptosis (caspase-1). These cell death mechanisms seem to be also related to the assembly of the inflammasome, which may, in turn, activate pro-inflammatory cytokines and chemokines. Thus, this particular molecular platform may play a crucial role in neuroinflammation mechanisms. Nowadays, a specific therapy is still lacking and the pathogenic mechanisms involving neuroinflammation and neuronal dysfunction have not yet been completely understood, making mevalonic aciduria an orphan drug disease. This review aims to analyze the relationship among neuroinflammation, mitochondrial damage, programmed cell death, and neurodegeneration. Targeting inflammation and degeneration in the central nervous system might help identify promising treatment approaches for mevalonic aciduria or other diseases in which these mechanisms are involved. Molecular Diversity Preservation International (MDPI) 2013-11-26 /pmc/articles/PMC3876043/ /pubmed/24287904 http://dx.doi.org/10.3390/ijms141223274 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Tricarico, Paola Maura
Marcuzzi, Annalisa
Piscianz, Elisa
Monasta, Lorenzo
Crovella, Sergio
Kleiner, Giulio
Mevalonate Kinase Deficiency and Neuroinflammation: Balance between Apoptosis and Pyroptosis
title Mevalonate Kinase Deficiency and Neuroinflammation: Balance between Apoptosis and Pyroptosis
title_full Mevalonate Kinase Deficiency and Neuroinflammation: Balance between Apoptosis and Pyroptosis
title_fullStr Mevalonate Kinase Deficiency and Neuroinflammation: Balance between Apoptosis and Pyroptosis
title_full_unstemmed Mevalonate Kinase Deficiency and Neuroinflammation: Balance between Apoptosis and Pyroptosis
title_short Mevalonate Kinase Deficiency and Neuroinflammation: Balance between Apoptosis and Pyroptosis
title_sort mevalonate kinase deficiency and neuroinflammation: balance between apoptosis and pyroptosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876043/
https://www.ncbi.nlm.nih.gov/pubmed/24287904
http://dx.doi.org/10.3390/ijms141223274
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