The Importance of Non-Coding RNAs in Neurodegenerative Processes of Diabetes-Related Molecular Pathways

Abstract

Diabetes mellitus (DM) is a complex condition and serious health problem, with growing occurrence of DM-associated complications occurring globally. Persistent hyperglycemia is confirmed as promoting neurovascular dysfunction leading to irreversible endothelial cell dysfunction, increased neuronal cell apoptosis, oxidative stress and inflammation. These collaboratively and individually result in micro- and macroangiopathy as well as neuropathy demonstrated by progressive neuronal loss. Recently, major efforts have been pursued to select not only useful diagnostic and prognostic biomarkers, but also novel therapeutic approaches. Both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) belong to a class of non-coding RNAs identified in most of the body fluids i.e., peripheral blood, cerebrospinal fluid, brain tissue and neurons. Numerous miRNAs, lncRNAs and their target genes are able to modulate signaling pathways known to play a role in the pathophysiology of progressive neuronal dysfunction. Therefore, they pose as promising biomarkers and treatment for the vast majority of neurodegenerative disorders. This review provides an overall assessment of both miRNAs' and lncRNAs' utility in decelerating progressive nervous system impairment, including neurodegeneration in diabetic pathways.

Keywords: biomarker; lncRNA; miR; miRNA; non-coding RNA; novel biomarker; treatment.

Figure 1

Diabetic corneal neuropathy. MiRNAs as promising therapeutics in diabetes-induced corneal degeneration. ↑ indicates the mimic-use as treatment, ↓ indicates inhibitor-use as treatment. Abbreviations: IL-1β, Interleukin 1β; TNF-α, Tumor necrosis factor α; MIAT, Myocardial infarction associated transcript; miRNA-miR, microRNA; lncRNA, long non-coding RNA.

Figure 2

Diabetic retinopathy. MiRNAs/lncRNAs as promising therapeutics in diabetes-induced retinal degeneration. ↑ indicates the mimic-use as treatment, ↓ indicates inhibitor-use as treatment. Abbreviations: GAS5, Growth arrest-specific transcript 5; IL-2, Interleukin 2; MIAT, Myocardial infarction associated transcript; NEAT1, Nuclear paraspeckle assembly transcript 1; RNCR3, Retinal non-coding RNA3, Sox2OT, Sox2 overlapping transcript; TNF-α, Tumor necrosis factor α; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; miRNA-miR, microRNA; lncRNA, long non-coding RNA.