MicroRNA networks surrounding APP and amyloid-尾 metabolism 鈥?Implications for Alzheimer's disease

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• 作者：Nicole Schonrock^a ; ^{n.schonrock@victorchang.edu.au} ; Miriam Matamales^b ; Lars M. Ittner^c ; Jü ; rgen Gö ; tz^b ; ^{juergen.goetz@sydney.edu.au}
• 关键词：Alzheimer ; A尾 (amyloid-尾) ; APP (amyloid precursor protein) ; Animal model ; BACE1 ; 尾-secretase ; MicroRNA ; Neurodegeneration ; Splicing ; Tau
• 刊名：Experimental Neurology
• 出版年：2012
• 期刊代码：78_00144886
• 类别：neu
• 出版时间：June, 2012
• 卷：235
• 期：2
• 页码：447-454
• 文件大小：627 K

摘要

MicroRNAs (miRNAs) are small non-coding RNA regulators of protein synthesis that function as 鈥渇ine-tuning鈥?tools of gene expression in development and tissue homeostasis. Their profiles are significantly altered in neurodegenerative diseases such as Alzheimer's disease (AD) that is characterized by both amyloid-尾 (A尾) and tau deposition in brain. A key challenge remains in determining how changes in miRNA profiles translate into biological function in a physiological and pathological context. The key lies in identifying specific target genes for deregulated miRNAs and understanding which pathogenic factors trigger their deregulation. Here we review the literature about the intricate network of miRNAs surrounding the regulation of the amyloid precursor protein (APP) from which A尾 is derived by proteolytic cleavage. Normal brain function is highly sensitive to any changes in APP metabolism and miRNAs function at several steps to ensure that the correct APP end product is produced and in the right form and abundance. Disruptions in this miRNA regulatory network may therefore alter A尾 production, which in turn can affect miRNA expression.