Inflammation and Apoptotic Pathways in the Peripheral Nervous System Related to Protein Misfolding

  • Maria João Saraiva

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant neurodegenerative disorder related to the systemic deposition of mutated transthyretin (TTR) amyloid fibrils, particularly in peripheral nervous system (PNS). Recently, evidence for the presence of toxic non-fibrillar TTR aggregates early in FAP nerves constituted a first step to unravel molecular signaling related to neurodegeneration in FAP. The toxic nature of TTR non-fibrillar aggregates, and not mature TTR fibrils, was evidenced by their ability to induce the expression of oxidative stress and inflammation-related molecules in neuronal cells, driving them into apoptotic pathways. How these TTR aggregates exert their effects is debatable; interaction with cellular receptors, namely the receptor for advanced glycation endproducts is a probable candidate mechanism. The pathology and the yet unknown molecular signaling mechanisms responsible for neurodegeneration in FAP will be discussed.


Amyloid Fibril Cardiac Amyloidosis Familial Amyloid Polyneuropathy Familial Amyloidotic Polyneuropathy Cryptic Epitope 
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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Maria João Saraiva
    • 1
  1. 1.Molecular Neurobiology, IBMC & ICBASUniversity of PortoPortugal

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