Glial cells in familial amyloidotic polyneuropathy.

ABSTRACT

INTRODUCTION: 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.