Li S, Mallory M, Alford M, Tanaka S, Masliah E
University of California, San Diego, School of Medicine, Department of Neurosciences, La Jolla 92093-0624, USA.
J Neuropathol Exp Neurol. 1997 Aug;56(8):901-11. doi: 10.1097/00005072-199708000-00008.
Recent studies have shown that deficient functioning of glutamate transporters (GTs) in Alzheimer disease (AD) might lead to neurodegeneration. The main objectives of the present study were to determine which GT subtype is most affected in AD and to asses to what extent altered GT function is associated with abnormal amyloid precursor protein (APP) expression. While EAAT2-immunoreactivity (IR) was decreased in AD frontal cortex, EAAT1- and EAAT3-IR were unaffected; mRNA levels for all 3 GTs were not affected. Decreased EAAT2-IR was associated with decreased GT activity. EAAT2-IR inversely correlated with EAAT2 mRNA levels, suggesting that in AD, GT expression alterations occur due to disturbance at the post-transcriptional level. EAAT2-IR was inversely correlated with APP770 mRNA. In addition, GT activity directly correlated with APP695 mRNA and total APP protein levels, and inversely correlated with APP751/770 mRNA levels. This study supports the notion that astroglial EAAT2 is affected in AD and abnormal functioning and/or processing of APP might play an important role in this process.
最近的研究表明，阿尔茨海默病（AD）中谷氨酸转运体（GTs）功能缺陷可能导致神经退行性变。本研究的主要目的是确定哪种GT亚型在AD中受影响最大，并评估GT功能改变与淀粉样前体蛋白（APP）异常表达的相关程度。虽然AD额叶皮质中EAAT2免疫反应性（IR）降低，但EAAT1和EAAT3-IR未受影响；所有3种GT的mRNA水平均未受影响。EAAT2-IR降低与GT活性降低相关。EAAT2-IR与EAAT2 mRNA水平呈负相关，表明在AD中，GT表达改变是由于转录后水平的干扰所致。EAAT2-IR与APP770 mRNA呈负相关。此外，GT活性与APP695 mRNA和总APP蛋白水平直接相关，与APP751/770 mRNA水平呈负相关。本研究支持这样一种观点，即星形胶质细胞EAAT2在AD中受到影响，APP的异常功能和/或加工可能在此过程中起重要作用。
