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Interleukin-1 signaling pathway as a therapeutic target in transthyretin amyloidosis.

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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01071597
Contributor : Marie-Christine Vougny <>
Submitted on : Monday, October 6, 2014 - 11:59:08 AM
Last modification on : Monday, January 13, 2020 - 5:08:07 PM

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Nádia Pereira Gonçalves, Paulo Vieira, Maria João Saraiva. Interleukin-1 signaling pathway as a therapeutic target in transthyretin amyloidosis.. Amyloid: The Journal of Protein Folding Disorders, Taylor & Francis, 2014, 21 (3), pp.175-84. ⟨10.3109/13506129.2014.927759⟩. ⟨pasteur-01071597⟩

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