Interleukin-1 Signaling Pathway as a Therapeutic Target in Transthyretin Amyloidosis

Amyloid. 2014 Sep;21(3):175-84. doi: 10.3109/13506129.2014.927759. Epub 2014 Jun 11.


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.

Keywords: Anakinra; cytokines; familial amyloidotic polyneuropathy; neurodegeneration; neuroinflammation; peripheral nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Neuropathies, Familial / drug therapy*
  • Amyloid Neuropathies, Familial / immunology
  • Amyloid Neuropathies, Familial / pathology
  • Animals
  • Apoptosis
  • Disease Models, Animal
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / immunology
  • Ganglia, Spinal / pathology
  • Gene Expression
  • Injections, Subcutaneous
  • Interleukin 1 Receptor Antagonist Protein / pharmacology*
  • Interleukin-1beta / antagonists & inhibitors*
  • Interleukin-1beta / immunology
  • Mice
  • Mice, Transgenic
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / immunology
  • Nerve Fibers, Unmyelinated / pathology
  • Oxidative Stress
  • Prealbumin / chemistry*
  • Prealbumin / genetics
  • Protein Aggregates
  • Protein Aggregation, Pathological / drug therapy*
  • Protein Aggregation, Pathological / immunology
  • Protein Aggregation, Pathological / pathology
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / immunology
  • Sciatic Nerve / pathology
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology
  • Transgenes


  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Prealbumin
  • Protein Aggregates

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related