Role of non-coding RNAs in non-aging-related neurological disorders

Abstract

Protein coding sequences represent only 2% of the human genome. Recent advances have demonstrated that a significant portion of the genome is actively transcribed as non-coding RNA molecules. These non-coding RNAs are emerging as key players in the regulation of biological processes, and act as "fine-tuners" of gene expression. Neurological disorders are caused by a wide range of genetic mutations, epigenetic and environmental factors, and the exact pathophysiology of many of these conditions is still unknown. It is currently recognized that dysregulations in the expression of non-coding RNAs are present in many neurological disorders and may be relevant in the mechanisms leading to disease. In addition, circulating non-coding RNAs are emerging as potential biomarkers with great potential impact in clinical practice. In this review, we discuss mainly the role of microRNAs and long non-coding RNAs in several neurological disorders, such as epilepsy, Huntington disease, fragile X-associated ataxia, spinocerebellar ataxias, amyotrophic lateral sclerosis (ALS), and pain. In addition, we give information about the conditions where microRNAs have demonstrated to be potential biomarkers such as in epilepsy, pain, and ALS.

Circulating nucleic acids in the plasma and serum as potential biomarkers in neurological disorders

“…cfRNAs can be classified as protein-coding (mRNAs) or non-coding RNAs. Non-coding RNAs are further classified according to size as small non-coding RNAs (sncRNAs), including microRNAs and lncRNAs ( 35 , 36 ). The most recent studies that investigated the application of cfRNAs as biomarkers in plasma and serum have focused on non-coding RNAs, especially microRNAs ( 35 ).…”

“…An interesting aspect of microRNA-mediated gene regulation is its complexity: a single microRNA can regulate many mRNAs, and one mRNA can be regulated by multiple microRNAs ( 39 ). Although RNA molecules are relatively unstable and susceptible to degradation by Rnases – a protein superfamily generally abundant in biofluids ( 10 ) – studies have shown that microRNAs are particularly stable and resistant to nuclease digestion in the plasma and serum ( 24 , 35 , 36 ). Thus, microRNAs represent an easily assayed molecule.…”

“…In addition, small molecules, such as microRNAs, can cross the BBB and enter the circulation; therefore, biological processes that occur in the CNS can be reflected by the pattern and amount of brain-derived microRNAs in peripheral blood ( 3 ). MicroRNAs have been associated with the normal function and development of the nervous system as well as neurological disorders ( 36 , 42 , 43 ). While several studies regarding the use of cf-microRNAs as biomarkers have been published (Supplementary Table S1), there is still much to discover.…”

“…As discussed above, biological changes may be reflected in cf-microRNA levels, a phenomenon that makes these species attractive biomarkers for diseases. Furthermore, cf-microRNA levels can be easily quantifiable by RT-qPCR or even by high-throughput techniques, such as microarray or RNA sequencing (RNA-seq) ( 35 , 36 ) ( Figure 3 ). However, the cf-microRNA abundance might be influenced by different biological aspects, such as sex, age, secondary disease, drug treatment, etc.…”

Silencing of lncRNA PKIA-AS1 Attenuates Spinal Nerve Ligation-Induced Neuropathic Pain Through Epigenetic Downregulation of CDK6 Expression

“…Non-coding RNAs (ncRNAs), including microRNAs and long non-coding RNAs (lncRNAs), contribute to diverse biological processes by regulating the expression of mRNA targets at the post-transcriptional level (Bali and Kuner, 2014; Zhou et al, 2017) by targeting several pain pathways (Tan et al, 2015; Plassais et al, 2016; Shao et al, 2018). Dysregulation of non-coding RNAs has also been implicated in the development of neuropathic pain (Liu et al, 2017; Vieira et al, 2018). For example, lncRNA BC168687 is associated with diabetic neuropathic pain (Liu et al, 2018), while lncRNA MRAK009713, NEAT1, and XIST can regulate chronic constriction injury-induced neuropathic pain (Li et al, 2017; Xia et al, 2018; Yan et al, 2018).…”