The role of astrocytes in amyloid 尾-protein toxicity and clearance
- 作者：Dietmar Rudolf Thal ; Dietmar.Thal@uni-ulm.de
- 关键词：Astrocytes ; Amyloid 尾-protein ; Apolipoprotein E ; Clearance ; Toxicity ; Blood&ndash ; brain barrier ; LRP1
- 刊名：Experimental Neurology
- 出版年：2012
- 期刊代码：78_00144886
- 类别：neu
- 出版时间：July, 2012
- 卷：236
- 期：1
- 页码：1-5
- 文件大小：319 K
摘要
The deposition of the amyloid 尾-protein (A尾) in the brain is a pathological hallmark of Alzheimer's disease (AD). Here, A尾 deposits occur as A尾 plaques in the brain parenchyma and in the walls of cerebral and leptomenigeal blood vessels. Astrocytes are considered to be involved in the clearance of A尾 from the brain parenchyma into the perivascular space, across the blood-brain barrier, or by enzymatic degradation. As such it has been assumed that clearance of A尾 by astrocytes is beneficial. In a recent study published in Experimental Neurology Mulder et al. (2012; 233: 373-379) report changes in neprilysin and scavenger receptor class B member 1 gene expression in astrocytes exposed to fibrillar A尾 depending on the availability of amyloid-associated proteins, especially apolipoprotein E (apoE). Astrocytes from AD patients did not show this response in gene expression. Reactive astrocytes and A尾 containing astrocytes are common findings in the AD brain. A loss of excitatory amino acid transporter 2 expression in perivascular astrocytes of APOE 蔚4-positive AD cases and an alteration of neuronal apoE metabolism in the event of perivascular drainage of apoE-A尾 complexes has also been described. As such, reactive and compensatory changes in AD astrocytes compete with supporting functions of astrocytes finally leading to an impairment of metabolic support and transmitter recycling in the brain. In summary, exposure of astrocytes to increased amounts of A尾 over a long period in time very likely impairs the above mentioned supporting functions of astrocytes in AD patients because these cells have to clear large amounts of A尾 and, thereby, neglect their other functions.