The Regulation of microRNAs in Alzheimer's Disease

Abstract

MicroRNAs are small non-coding nucleic acids that are responsible for regulating the gene expression by binding to the coding region and 3' and 5' un-translated region of target messenger RNA. Approximately 70% of known microRNAs are expressed in the brain and increasing evidences demonstrate the possible involvement of microRNAs in Alzheimer's disease (AD) according to the statistics. The characteristic symptoms of AD are the progressive loss of memory and cognitive functions due to the deposition of amyloid β (Aβ) peptide, intracellular aggregation of hyperphosphorylated Tau protein, the loss of synapses, and neuroinflammation, as well as dysfunctional autophagy. Therefore, microRNA-mediated regulation for above-mentioned changes may be the potential therapeutic strategies for AD. In this review, the role of specific microRNAs involved in AD and corresponding applications are systematically discussed, including positive effects associated with the reduction of Aβ or Tau protein, the protection of synapses, the inhibition of neuroinflammation, the mitigation of aging, and the induction of autophagy in AD. It will be beneficial to develop effective targets for establishing a cross link between pharmacological intervention and AD in the near future.

Serum miR-128 Serves as a Potential Diagnostic Biomarker for Alzheimer’s Disease

“…MicroRNAs (miRNAs) are a group of small noncoding RNAs with vital regulatory roles in gene expression. 4 Recently, aberrant changes in miRNAs have been discovered to participate in AD progression, and are considered candidate blood-based biomarkers of AD, as they have been found to guide the clinical diagnosis of AD. 5 , 6 Wang et al 7 reported that the expression levels of miR-433 were reduced in AD patients and that this miRNA has the potential to be a therapeutic target through improving Aβ-induced neurotoxicity.…”

microRNA-Based Biomarkers in Alzheimer’s Disease (AD)

“…These findings support the strengthening contention: (i) that brain-enriched miRNAs operate as fundamental components of an epigenetically controlled post-transcriptional signaling network in the mammalian CNS Kleaveland et al, 2018;Jaber et al, 2019;Eisen et al, 2020); and (ii) that miRNAs have an established capability to act independently, coordinately and/or cooperatively to create a highly sophisticated and interactive regulatory miRNA-mRNA network for families of brain genes that regulate many essential brain functions that are specifically altered in AD brain (Jaber et al, 2017;Kleaveland et al, 2018;Eisen et al, 2020;Lukiw, 2020a,b). Importantly, information-carrying ribonucleic acids such as highly soluble and mobile, single-stranded non-coding RNAs (sncRNAs) including microRNAs (miRNAs) can affect the operation of a large number of highly interactive pathogenic signaling pathways in the CNS, and represent strategic candidates for promoting AD onset, and for modulating or maintaining AD propagation and disease spread (Alexandrov et al, 2012;Chandrasekaran and Bonchev, 2016;Clement et al, 2016;Kleaveland et al, 2018;Lemcke and David, 2018;Hill, 2019;Jaber et al, 2019;Konovalova et al, 2019;Condrat et al, 2020;Fan et al, 2020;Kou et al, 2020).…”

“…Many miRNA signals appear to be non-specific biomarkers of brain cell atrophy, injury or death and inflammatory neurodegeneration, response to psychoactive medications or they may be associated with other non-AD pathologies that have gone undiagnosed or misdiagnosed (Figure 1). However, in combination with other specific biomarkers or diagnostic tools, the quantification of multiple species of miRNAs might be a useful part of the diagnostic puzzle to assist in the detection and discrimination of certain specific neurodegenerative disorders even though they may possess significant clinical overlap (Juźwik et al, 2019;Kou et al, 2020;Lukiw and Pogue, 2020;Ma et al, 2020). The analysis of miRNAs over time, such as in integrated studies of neurodevelopment in humans and in experimental transgenic animal models of AD (TgAD), have already been shown: (i) to be a promising tracer and prognostic biomarker for homeostatic brain function during normal brain development and neuronal differentiation from the embryonic period to adulthood (Giorgi Silveira et al, 2020); and (ii) in conjunction with extensive neuropsychological testing, may be further useful to monitor and predict the incidence of onset, the rate of progression of disease activity and its trajectory, and to further evaluate in detail both therapeutic responses and clinical efficacy (Peña-Bautista et al, 2019).…”

MicroRNAs at the Crossroad of the Dichotomic Pathway Cell Death vs. Stemness in Neural Somatic and Cancer Stem Cells: Implications and Therapeutic Strategies

“…It exceeds the purpose of this paper to describe the functions and potential applications of the numerous miRNAs in terms of diagnostic biomarkers since comprehensive reviews have been already written for AD [ 26 , 27 , 28 ] and PD [ 29 , 30 , 31 ], amyotrophic lateral sclerosis (ALS) [ 29 , 30 , 31 , 32 ], multiple sclerosis (MS) [ 33 , 34 ], traumatic brain injury (TBI) [ 35 , 36 ], or development-related syndromes, such as autism spectrum disorder (ASD) [ 37 , 38 ]. Instead, both in the central nervous system (CNS) and in the cerebral spinal fluid (CSF), miRNAs recruitment has boosted a novel impulse for the prognosis but, more strikingly, for neural regenerative medicine, shedding light on feasible translational brain applications that fill the present gap of clinical interventions represented by NSC transplantation.…”