Advanced

α-Synuclein pre-formed fibrils impair tight junction protein expression without affecting cerebral endothelial cell function

Kuan, Wei-Li; Bennett, Neal; He, Xiaoling; Skepper, Jeremy N; Martynyuk, Nataly; Wijeyekoon, Ruwani; Moghe, Prabhas V; Williams-Gray, Caroline H and Barker, Roger A LU (2016) In Experimental Neurology 285(Pt A). p.72-81
Abstract

Recently it has been shown that there is impaired cerebral endothelial function in many chronic neurodegenerative disorders including Alzheimer's and Huntington's disease. Such problems have also been reported in Parkinson's disease, in which α-synuclein aggregation is the pathological hallmark. However, little is known about the relationship between misfolded α-synuclein and endothelial function. In the present study, we therefore examined whether α-synuclein preformed fibrils affect endothelial function in vitro. Using a well-established endothelial cell model, we found that the expression of tight junction proteins, in particular zona occludens-1 and occludin, was significantly perturbed in the presence of fibril-seeded... (More)

Recently it has been shown that there is impaired cerebral endothelial function in many chronic neurodegenerative disorders including Alzheimer's and Huntington's disease. Such problems have also been reported in Parkinson's disease, in which α-synuclein aggregation is the pathological hallmark. However, little is known about the relationship between misfolded α-synuclein and endothelial function. In the present study, we therefore examined whether α-synuclein preformed fibrils affect endothelial function in vitro. Using a well-established endothelial cell model, we found that the expression of tight junction proteins, in particular zona occludens-1 and occludin, was significantly perturbed in the presence of fibril-seeded neurotoxicity. Disrupted expression of these proteins was also found in the postmortem brains of patients dying with Parkinson's disease. There was though little evidence in vitro of functional impairments in endothelial cell function in terms of transendothelial electrical resistance and permeability. This study therefore shows for the first time that misfolded α-synuclein can interact and affect the cerebral endothelial system, although its relevance to the pathogenesis of Parkinson's disease remains to be elucidated.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Neurology
volume
285
issue
Pt A
pages
10 pages
publisher
Academic Press
external identifiers
  • scopus:84987933108
ISSN
0014-4886
DOI
10.1016/j.expneurol.2016.09.003
language
English
LU publication?
no
id
ad9961c8-925f-4821-8861-c401ff9b16de
date added to LUP
2016-11-23 13:04:28
date last changed
2017-01-01 08:40:26
@article{ad9961c8-925f-4821-8861-c401ff9b16de,
  abstract     = {<p>Recently it has been shown that there is impaired cerebral endothelial function in many chronic neurodegenerative disorders including Alzheimer's and Huntington's disease. Such problems have also been reported in Parkinson's disease, in which α-synuclein aggregation is the pathological hallmark. However, little is known about the relationship between misfolded α-synuclein and endothelial function. In the present study, we therefore examined whether α-synuclein preformed fibrils affect endothelial function in vitro. Using a well-established endothelial cell model, we found that the expression of tight junction proteins, in particular zona occludens-1 and occludin, was significantly perturbed in the presence of fibril-seeded neurotoxicity. Disrupted expression of these proteins was also found in the postmortem brains of patients dying with Parkinson's disease. There was though little evidence in vitro of functional impairments in endothelial cell function in terms of transendothelial electrical resistance and permeability. This study therefore shows for the first time that misfolded α-synuclein can interact and affect the cerebral endothelial system, although its relevance to the pathogenesis of Parkinson's disease remains to be elucidated.</p>},
  author       = {Kuan, Wei-Li and Bennett, Neal and He, Xiaoling and Skepper, Jeremy N and Martynyuk, Nataly and Wijeyekoon, Ruwani and Moghe, Prabhas V and Williams-Gray, Caroline H and Barker, Roger A},
  issn         = {0014-4886},
  language     = {eng},
  number       = {Pt A},
  pages        = {72--81},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {α-Synuclein pre-formed fibrils impair tight junction protein expression without affecting cerebral endothelial cell function},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2016.09.003},
  volume       = {285},
  year         = {2016},
}