Interleukin-1 signaling pathway as a therapeutic target in transthyretin amyloidosis.
Identifieur interne : 000763 ( Main/Exploration ); précédent : 000762; suivant : 000764Interleukin-1 signaling pathway as a therapeutic target in transthyretin amyloidosis.
Auteurs : Nádia Pereira Gonçalves [Portugal] ; Paulo Vieira [France] ; Maria João Saraiva [Portugal]Source :
- Amyloid [ 1350-6129 ] ; 2014-09.
English descriptors
- mix :
Abstract
INTRODUCTION: Inflammation is a key pathological hallmark of several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and familial amyloidotic polyneuropathy (FAP). Among all inflammatory cytokines associated with FAP, IL-1β, in particular, has been implicated in playing a key pathogenic role. In the present study, we sought to investigate whether blocking IL-1β signaling provides disease-modifying benefits in an FAP mouse model. METHODS: We assessed the effect of chronic administration of Anakinra, an IL-1 antagonist, on FAP pathogenesis in vivo, using real-time polymerase chain reaction (qPCR), semi-quantitative immunohistochemistry (SQ-IHC), western blot and nerve morphometric analyses. RESULTS: We found that treatment with Anakinra prevents transthyretin (TTR) extracellular deposition in sciatic nerve, protecting unmyelinated nerve fibers from aggregate-induced degeneration. Moreover, Anakinra administration significantly suppressed IL-1 signaling pathway and inhibited apoptosis and nitrative stress. CONCLUSIONS: The present work highlights the relevance of the IL-1 signaling pathway in the pathophysiology of FAP. Our results bring to light the importance of non-amyloid targets in the therapeutic strategies for this disorder. Thus, we propose the use of Anakinra as a potential therapeutic agent for TTR-related amyloidosis.
Url:
DOI: 10.3109/13506129.2014.927759
Affiliations:
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Le document en format XML
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type="DOI">10.3109/13506129.2014.927759</idno><series><title level="j">Amyloid</title><idno type="ISSN">1350-6129</idno><imprint><date type="datePub">2014-09</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>Anakinra</term><term>cytokines</term><term>familial amyloidotic</term><term>neurodegeneration</term><term>neuroinflammation</term><term>peripheral nervous system</term><term>polyneuropathy</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">INTRODUCTION: Inflammation is a key pathological hallmark of several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and familial amyloidotic polyneuropathy (FAP). Among all inflammatory cytokines associated with FAP, IL-1β, in particular, has been implicated in playing a key pathogenic role. In the present study, we sought to investigate whether blocking IL-1β signaling provides disease-modifying benefits in an FAP mouse model. METHODS: We assessed the effect of chronic administration of Anakinra, an IL-1 antagonist, on FAP pathogenesis in vivo, using real-time polymerase chain reaction (qPCR), semi-quantitative immunohistochemistry (SQ-IHC), western blot and nerve morphometric analyses. RESULTS: We found that treatment with Anakinra prevents transthyretin (TTR) extracellular deposition in sciatic nerve, protecting unmyelinated nerve fibers from aggregate-induced degeneration. Moreover, Anakinra administration significantly suppressed IL-1 signaling pathway and inhibited apoptosis and nitrative stress. CONCLUSIONS: The present work highlights the relevance of the IL-1 signaling pathway in the pathophysiology of FAP. Our results bring to light the importance of non-amyloid targets in the therapeutic strategies for this disorder. Thus, we propose the use of Anakinra as a potential therapeutic agent for TTR-related amyloidosis.</div></front></TEI><affiliations><list><country><li>France</li><li>Portugal</li></country></list><tree><country name="Portugal"><noRegion><name sortKey="Goncalves, Nadia Pereira" sort="Goncalves, Nadia Pereira" uniqKey="Goncalves N" first="Nádia Pereira" last="Gonçalves">Nádia Pereira Gonçalves</name></noRegion><name sortKey="Saraiva, Maria Joao" sort="Saraiva, Maria Joao" uniqKey="Saraiva M" first="Maria João" last="Saraiva">Maria João Saraiva</name></country><country name="France"><noRegion><name sortKey="Vieira, Paulo" sort="Vieira, Paulo" uniqKey="Vieira P" first="Paulo" last="Vieira">Paulo Vieira</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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