MicroRNA Alteration, Application as Biomarkers, and Therapeutic Approaches in Neurodegenerative Diseases

Abstract

MicroRNAs (miRNAs) are essential post-transcriptional gene regulators involved in various neuronal and non-neuronal cell functions and play a key role in pathological conditions. Numerous studies have demonstrated that miRNAs are dysregulated in major neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, or Huntington's disease. Hence, in the present work, we constructed a comprehensive overview of individual microRNA alterations in various models of the above neurodegenerative diseases. We also provided evidence of miRNAs as promising biomarkers for prognostic and diagnostic approaches. In addition, we summarized data from the literature about miRNA-based therapeutic applications via inhibiting or promoting miRNA expression. We finally identified the overlapping miRNA signature across the diseases, including miR-128, miR-140-5p, miR-206, miR-326, and miR-155, associated with multiple etiological cellular mechanisms. However, it remains to be established whether and to what extent miRNA-based therapies could be safely exploited in the future as effective symptomatic or disease-modifying approaches in the different human neurodegenerative disorders.

Keywords: Alzheimer’s disease (AD); Huntington’s disease (HD); Parkinson’s disease (PD); amyotrophic lateral sclerosis (ALS); biomarker; dysregulation; microRNAs (miRNAs); multiple sclerosis (MS); neurodegenerative diseases.

Figure 1

Complexity of the links between different miRNAs and molecular pathways–targets involved in neurodegenerative diseases.

Figure 2

miRNA interconnection among NDs. ↑: upregulated; ↓: downregulated.