文章基本信息

标题：Ribonucleoprotein Therapy in Alzheimer's Disease?
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作者：Je-Hyun Yoon ; Myriam Gorospe
期刊名称：Aging
出版年度：2014
卷号：6
期号：6
页码：428-429
出版社：U.S.Department of Health & Human Service
摘要：Age-related neurodegenerative pathologies like Alzheimer's and Parkinson's diseases are accelerated by a decline in neuronal homeostasis. In this issue of Cell Reports, Kang et al. [1] reports the post-transcriptional mechanisms that regulate the expression and processing of amyloid precursor protein (APP), a protein directly implicated in the pathogenesis of Alzheimer's disease (AD). Although much is known about APP processing and cleavage, the post-transcriptional steps controlling APP biosynthesis are poorly defined. The important advance by Kang et al. 2014 is discovering that a single RNA-binding protein (RBP), HuD, binds to APP mRNA and enhances its stability and translation in cells of neuronal origin, stabilizes BACE1 mRNA, encoding the ¦Â-site APP-cleaving enzyme 1 (BACE1), and stabilizes BACE1 antisense (BACE1AS), a long noncoding (lnc) RNA that protects BACE1 mRNA from degradation. The positive influence of HuD on these RNAs and the encoded proteins was documented in the brains of mice overexpressing HuD as well as in patients with Alzheimer's Disease, and was linked to the accumulation of the toxic APP cleavage product A¦Â in these systems. The results underscore a novel function for HuD in neurodegeneration through its regulation of RNA targets controlling A¦Â production. Given its joint influence on three functionally linked RNAs (APP mRNA, BACE1 mRNA, and BACE1AS), that contribute to generating the neurotoxic peptide A¦Â, HuD emerges from the studies by Kang and colleagues as a single factor that promotes APP processing to A¦Â. Such a coordinated influence on a cellular function by a single RBP represents an example of the post- transcriptional operon/regulon proposed by Keene and Tenenbaum [2].