血液脳関門におけるαシヌクレインの取り込み特性

• Published in: 日本薬理学会年会要旨集 p. 3-B-P-230
• Main Authors: 横谷, みき, 高田, 芙友子, 佐野, 和憲, 松本, 純一, 岩尾, 卓朗, 道具, 伸也
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: blood-brain barrier; endothelial cell; neurodegeneration; transporter
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_3-B-P-230

Parkinson disease (PD) is characterized by widespread distribution of aggregated α-synuclein (α-Syn) protein in inclusions known as Lewy bodies. α-Syn is secreted from neurons and transferred to neighboring cells. This cell-to-cell transmission is thought to underlie the progress of PD. In addition, it is known that blood α-Syn levels in patients with PD are elevated and blood-borne α-Syn can penetrate into the brain across the blood-brain barrier (BBB). Therefore, another explanation for elevated brain levels of α-Syn is the increased transport of α-Syn from blood to brain across the BBB. Here, we investigated how monomeric α-Syn is taken up by brain endothelial cells which constitute the BBB. We assessed uptake of α-Syn by brain endothelial cells as cell/medium ratio using primary cultures of rat brain endothelial cells (RBECs). Increasing concentrations of α-Syn resulted in the increased cellular accumulation of α-Syn in RBECs. The cell/medium ratio did not show significant changes with the increased concentration of extracellular α-Syn ranging from 0.05 to 10 μg/mL, suggesting that α-Syn uptake by RBECs is independent of a saturable transport system. However, the α-Syn uptake by RBECs showed a temperature-dependent manner, suggesting that α-Syn uptake by RBECs is mediated by an energy-dependent transport system. This uptake was inhibited by mannan. These results suggest that α-Syn transport at the BBB would be mediated by a mannan-sensitive transport system including mannose receptor-mediated transcytosis.