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

作者：Kuan Wei Li^*; Bennett Neal; He Xiaoling; Skepper Jeremy N; Martynyuk Nataly; Wijeyekoon Ruwani; Moghe Prabhas V; Williams Gray Caroline H; Barker Roger A

来源：Experimental Neurology, 2016, 285: 72-81.

DOI：10.1016/j.expneurol.2016.09.003

• alpha-Synuclein preformed fibrils
• Blood-brain barrier
• Transendothelial electrical resistance
• Permeability
• Zona occludens-1
• Occludin
• Parkinson's disease

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 alpha-synuclein aggregation is the pathological hallmark. However, little is known about the relationship between misfolded alpha-synuclein and endothelial function. In the present study, we therefore examined whether alpha-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 alpha-synuclein can interact and affect the cerebral endothelial system, although its relevance to the pathogenesis of Parkinson's disease remains to be elucidated.

• 出版日期2016-11