title: Glial cells in familial amyloidotic polyneuropathy.
abstract: BACKGROUND
  Transthyretin V30M mutation is the most common variant leading to Familial Amyloidotic Polyneuropathy. In this genetic disorder, Transthyretin accumulates preferentially in the extracellular matrix of peripheral and autonomic nervous systems leading to cell death and dysfunction. Thus, knowledge regarding important biological systems for Transthyretin clearance might unravel novel insights into Familial Amyloidotic Polyneuropathy pathophysiology. Herein, our aim was to evaluate the ability of glial cells from peripheral and autonomic nervous systems in Transthyretin uptake and degradation. We assessed the role of glial cells in Familial Amyloidotic Polyneuropathy pathogenesis with real-time polymerase chain reaction, immunohistochemistry, interference RNA and confocal microscopy.
  
  
  RESULTS
  Histological examination revealed that Schwann cells and satellite cells, from an Familial Amyloidotic Polyneuropathy mouse model, internalize and degrade non-fibrillar Transthyretin. Immunohistochemical studies of human nerve biopsies from V30M patients and disease controls showed intracellular Transthyretin immunoreactivity in Schwann cells, corroborating animal data. Additionally, we found Transthyretin expression in colon of this Familial Amyloidotic Polyneuropathy mouse model, probably being synthesized by satellite cells of the myenteric plexus.
  
  
  CONCLUSIONS
  Glial cells from the peripheral and autonomic nervous systems are able to internalize Transthyretin. Overall, these findings bring to light the closest relationship between Transthyretin burden and clearance from the nervous system extracellular milieu.
authors.forename: Nádia P
authors.initials: NP
authors.lastname: Gonçalves
authors.forename: Susete
authors.initials: S
authors.lastname: Costelha
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Saraiva
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009197:Myenteric Plexus / Q000378:metabolism; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism*; D027161:Satellite Cells, Perineuronal / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism*; D013497:Sural Nerve / Q000378:metabolism
chemical_list: D011228:Prealbumin