microRNA (miRNA)-Mediated Pathogenetic Signaling in Alzheimer's Disease (AD)
microRNA (miRNA)-Mediated Pathogenetic Signaling in Alzheimer's Disease (AD)
复制标题
DOI：
10.1007/s11064-015-1734-7
复制
发表时间：
2016-02-01
影响因子：
4.4
通讯作者：
Lukiw, Walter J.
中科院分区：
文献类型：
--
作者：
Hill, James M.;Lukiw, Walter J.
阿尔茨海默病(AD)在工业化社会中是一个日益严重的健康和社会经济问题，也是我们老龄化人口中智力障碍的主要原因。阿尔茨海默病的病因尚不清楚，目前还没有有效的治疗方法来阻止或逆转这种独特的人类和年龄相关的神经疾病的发展。阐明AD的机制和导致这种慢性和致命神经变性的开始、进展和扩散的因素最终将导致改进和有效的诊断和治疗策略。microRNAs(MiRNAs)包括一类相对最近发现的20-24核苷酸非编码RNA，它们在转录后塑造细胞的转录组，从而有助于人类中枢神经系统健康和疾病的分子遗传学和表型。到目前为止，大约有2550个独特的成熟人类miRNA已被鉴定，然而只有高度选择的miRNA群体似乎丰富在CNS内的不同解剖区段。这篇为《特刊：神经化学研究的40年》的总评将介绍(I)关于CNS miRNA在AD和人脑老化中非凡的生物物理和信号特性的一些最新发现；(Ii)miRNAs的特定内在生物物理属性如何在AD表型的建立、增殖和传播中发挥决定性作用；以及(Iii)miRNAs如何作为预期的治疗靶点和生物标记物，在这种终末期神经疾病的临床管理中具有潜在的有用作用，这种疾病在我们迅速老龄化的人口中的发病率正在达到流行病的比例。
Alzheimer's disease (AD) is an expanding health and socioeconomic concern in industrialized societies, and the leading cause of intellectual impairment in our aging population. The cause of AD remains unknown, and there are currently no effective treatments to stop or reverse the progression of this uniquely human and age-related neurological disorder. Elucidation of the AD mechanism and factors that contribute to the initiation, progression, and spreading of this chronic and fatal neurodegeneration will ultimately result in improved and effective diagnostics and therapeutic strategies.microRNAs (miRNAs) comprise a relatively recently discovered category of 20-24 nucleotide non-coding RNAs that function post-transcriptionally in shaping the transcriptome of the cell, and in doing so, contribute to the molecular-genetics and phenotype of human CNS health and disease. To date about 2550 unique mature human miRNAs have been characterized, however only highly selected miRNA populations appear to be enriched in different anatomical compartments within the CNS.This general commentary for the 'Special Issue: 40th Year of Neurochemical Research' will bring into perspective (i) some very recent findings on the extraordinary biophysics and signaling properties of CNS miRNA in AD and aging human brain; (ii) how specific intrinsic biophysical attributes of miRNAs may play defining roles in the establishment, proliferation and spreading of the AD phenotype; and (iii) how miRNAs can serve as prospective therapeutic targets and biomarkers potentially useful in the clinical management of this terminal neurological disease whose incidence in our rapidly aging population is reaching epidemic proportions.