MS and Stem Cell Group, Translational Health Sciences, Bristol Medical School, University of Bristol, UK.
Dementia Research Group, Translational Health Sciences, Bristol Medical School, University of Bristol, UK.
J Alzheimers Dis. 2017;60(4):1511-1524. doi: 10.3233/JAD-170094.
Defects in motor protein-mediated neuronal transport mechanisms have been implicated in a number of neurodegenerative disorders but remain relatively little studied in Alzheimer's disease (AD). Our aim in the present study was to assess the expression of the anterograde kinesin superfamily motor proteins KIF5A, KIF1B, and KIF21B, and to examine their relationship to levels of hyperphosphorylated tau, amyloid-β protein precursor (AβPP), and amyloid-β (Aβ) in human brain tissue. We used a combination of qPCR, immunoblotting, and ELISA to perform these analyses in midfrontal cortex from 49 AD and 46 control brains. Expression of KIF5A, KIF1B, and KIF21B at gene and protein level was significantly increased in AD. KIF5A protein expression correlated inversely with the levels of AβPP and soluble Aβ in AD brains. Upregulation of KIFs may be an adaptive response to impaired axonal transport in AD.
运动蛋白介导的神经元运输机制缺陷与许多神经退行性疾病有关，但在阿尔茨海默病（AD）中研究相对较少。本研究旨在评估顺行驱动蛋白超家族运动蛋白 KIF5A、KIF1B 和 KIF21B 的表达，并研究其与人类脑组织中过度磷酸化 tau、淀粉样前体蛋白（AβPP）和淀粉样蛋白-β（Aβ）水平的关系。我们使用 qPCR、免疫印迹和 ELISA 组合在 49 例 AD 和 46 例对照大脑的额中回进行了这些分析。AD 患者的 KIF5A、KIF1B 和 KIF21B 在基因和蛋白水平的表达均显著增加。AD 大脑中 KIF5A 蛋白表达与 AβPP 和可溶性 Aβ 水平呈负相关。KIFs 的上调可能是 AD 中轴突运输受损的适应性反应。
