神经科学
血脑屏障
淀粉样蛋白(真菌学)
体外
BETA(编程语言)
医学
化学
生物
中枢神经系统
病理
生物化学
计算机科学
程序设计语言
作者
Kseniya B. Varshavskaya,Irina Yu. Petrushanko,Vladimir A. Mitkevich,Evgeny P. Barykin,Alexander А. Makarov
标识
DOI:10.3389/fnmol.2024.1362581
摘要
One of the hallmarks of Alzheimer's disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ 42 containing isomerized Asp7 residue (iso-Aβ 42 ) and Aβ 42 containing phosphorylated Ser8 residue (pS8-Aβ 42 ) crossed the BBB better than unmodified Aβ 42 , which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ 42 an order of magnitude weaker than to Aβ 42 . Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.
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