Overexpression of Protocadherin-10 in Transthyretin-Related Familial Amyloidotic Polyneuropathy.

Overexpression of Protocadherin-10 in Transthyretin-Related Familial Amyloidotic Polyneuropathy. Am J Pathol. 2016 Jul;186(7):1913-24 Authors: Gonçalves NP, Martins D, Saraiva MJ Abstract Overwhelming data suggest that oncogenic and neurodegenerative pathways share several altered cellular responses to insults such as oxidative stress, extracellular matrix remodeling, inflammation, or cell dyscommunication. Protocadherin-10 (Pcdh10) is an adhesion molecule found to protect against tumorigenesis and essential for axonal elongation and actin dynamics during development. Here, by using genome microarrays we identified for the first time Pcdh10 up-regulation in tissues from transgenic mouse models, cultured Schwann cells, and human samples from a familial form of peripheral neuropathy (familial amyloidotic polyneuropathy). Familial amyloidotic polyneuropathy is characterized by poor functional recovery and impaired nerve regenerative response after misfolding and deposition in the peripheral nervous system of mutant transthyretin. Not only increased transcriptional and translational Pcdh10 levels occurred in axons and Schwann cells of nerves with deposited transthyretin aggregates but the pattern also extended to associated cues of axon guidance like neuropilin-1 and F-actin. These findings suggest that Pcdh10 may influence subcellular actin cytoskeletal organization and axon-axon interactions in the course of familial amyloidotic polyn...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research