MicroRNAs (miRNAs) in Neurodegenerative Diseases

Abstract

Aging-related neurodegenerative diseases (NDs) are the culmination of many different genetic and environmental influences. Prior studies have shown that RNAs are pathologically altered during the inexorable course of some NDs. Recent evidence suggests that microRNAs (miRNAs) may be a contributing factor in neurodegeneration. miRNAs are brain-enriched, small (~22 nucleotides) non-coding RNAs that participate in mRNA translational regulation. Although discovered in the framework of worm development, miRNAs are now appreciated to play a dynamic role in many mammalian brain-related biochemical pathways, including neuroplasticity and stress responses. Research about miRNAs in the context of neurodegeneration is accumulating rapidly, and the goal of this review is to provide perspective for these new data that may be helpful to specialists in either field. An overview is provided about the normal functions for miRNAs, including some of the newer concepts related to the human brain. Recently published studies pertaining to the roles of miRNAs in NDs--including Alzheimer's disease, Parkinson's disease and triplet repeat disorders-are described. Finally, a discussion is included with theoretical syntheses and possible future directions in exploring the nexus between miRNA and ND research.

Structure of the dimerization domain of DiGeorge Critical Region 8

“…6 miRNAs have also been implicated in neurodegenerative diseases. 7 miRNAs are transcribed as long primary miRNAs (pri-miRNAs), which undergo sequential cleavage steps in the nucleus and cytoplasm. [8][9][10] In the first step, a pri-miRNA is cleaved into a $65-nt intermediate, termed precursor miRNAs (pre-miRNAs), by the combined action of an RNase III enzyme Drosha 11 and an RNA-binding protein DiGeorge critical region 8 (DGCR8; the name in mammals; its fly and worm homologs are called Pasha and Pash-1, respectively).…”

Effect of a pre-microRNA-149 (miR-149) genetic variation on the risk of ischemic stroke in a Chinese Han population

“…miRNAs are known to play impor tant roles in many physiological and pathological processes, including tumorigenesis (Mocellin et al, 2009), proliferation (Johnnidis et al, 2008), hematopoiesis (Merkerova et al, 2008), metabolism (Aumiller and Förstemann, 2008), immune function (Carissimi et al, 2009), epigenetics, and neurodegenerative diseases (Bushati and Cohen, 2008). miRNAs have also been found to be beneficial for identifying the etiology of lymphoma (Lawrie et al, 2007) and progression of certain neurological diseases (Nelson et al, 2008). Over the past decade, miRNA microarray has been performed to examine the differential expression profiles of miRNAs in stroke in vivo and in vitro.…”

Non-Coding RNAs: A Dynamic and Complex Network of Gene Regulation

“…Depletion of Dicer which is involved in the biogenesis of microRNAs, in human cells leads to a significant enhancement of Ataxin-3-induced toxicity, which has been linked to neurodegeneration [61]. MicroRNAs may be contributing factors in neurodegeneration leading to Parkinson disease and Alzheimer disease [29,62]. Post-mortem brain studies of schizophrenics have revealed changes in the expression of certain proteins involved in synaptic neurotransmission and development.…”

“…Finally, the guide-strand confers specificity to the RISC that now recognizes mRNA targets that are in turn either degraded or translationally repressed [28]. Human microRNAs are typically expressed at high levels (1000-30,000 copies per cell), and can have profound impact on cellular physiology [29].…”