Decoding the non-coding RNAs in Alzheimer’s disease

Abstract

Non-coding RNAs (ncRNAs) are integral components of biological networks with fundamental roles in regulating gene expression. They can integrate sequence information from the DNA code, epigenetic regulation and functions of multimeric protein complexes to potentially determine the epigenetic status and transcriptional network in any given cell. Humans potentially contain more ncRNAs than any other species, especially in the brain, where they may well play a significant role in human development and cognitive ability. This review discusses their emerging role in Alzheimer's disease (AD), a human pathological condition characterized by the progressive impairment of cognitive functions. We discuss the complexity of the ncRNA world and how this is reflected in the regulation of the amyloid precursor protein and Tau, two proteins with central functions in AD. By understanding this intricate regulatory network, there is hope for a better understanding of disease mechanisms and ultimately developing diagnostic and therapeutic tools.

MicroRNA-181c Ameliorates Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats

“…Meanwhile, it is also reduced in the serum of AD risk factor models [40]. Schonrock et al [41] identify that miR-181c is downregulated in the hippocampal neuron cultures treated with Aβ 42 as well as in the hippocampus of Aβ 42 -depositing APP23 transgenic mice. Studies from Ivan group identify a set of hypoxia-regulated miRNAs (HRMs) in the cancer context, and miR-181c is increased in response to hypoxia in the breast and the colon cancer cells [16].…”

The interplay between microRNAs and histone deacetylases in neurological diseases

“…Indeed luciferase assays showed significant repression of SIRT1 with the addition of miR-9 or miR-181c. Interestingly, when both miR-9 and miR-181c were combined there was an additive effect on the luciferase repression (Schonrock and Götz, 2012). The activation of SIRT1 has previously been shown to delay aging and regulate the aggregation and removal of amyloid-beta (Cohen et al, 2004; Donmez et al, 2010; Qin et al, 2006).…”

Epigenetic mechanisms in Alzheimer's disease

“…There are excellent reviews on this subject, 32,33 and the interaction between epigenetic mechanisms and miRNAs has also been recently reviewed. 74 Here, only a brief summary is given of some of the important findings.…”

“…30 Furthermore, there is extensive evidence for anomalies, especially in the expression profile of miRNAs in neurodegenerative disorders, particularly AD. 28,[31][32][33] Long ncRNAs (200-100,000 nucleotides in length) are a heterogenous group forming the bulk of the human noncoding transcriptome. Various regulatory functions are assigned to them.…”