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Causes and Consequences of MicroRNA Dysregulation in Neurodegenerative Diseases

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Abstract

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS), originate from a loss of neurons in the central nervous system (CNS) and are severely debilitating. The incidence of neurodegenerative diseases increases with age, and they are expected to become more common due to extended life expectancy. Because of no clear mechanisms, these diseases have become a major challenge in neurobiology. It is well recognized that these disorders become the culmination of many different genetic and environmental influences. Prior studies have shown that microRNAs (miRNAs) are pathologically altered during the inexorable course of some neurodegenerative diseases, suggesting that miRNAs may be the contributing factor in neurodegeneration. Here, we review what is known about the involvement of miRNAs in the pathogenesis of neurodegenerative diseases. The biogenesis of miRNAs and various functions of miRNAs that act as the chief regulators will be discussed. We focus in particular on dysregulation of miRNAs which leads to several neurodegenerative diseases from three aspects: miRNA-generating disorders, miRNA-targeting genes and epigenetic alterations. Furthermore, recent evidences have shown that circulating miRNA expression levels are changed in patients with neurodegenerative diseases. Circulating miRNA expression levels are reported in patients in order to evaluate their application as biomarkers of these diseases. A discussion is included with a potential diagnostic biomarker and the possible future direction in exploring the nexus between miRNAs and various neurodegenerative diseases.

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Acknowledgments

This work was supported in part by grants from the National Natural Science Foundation of China (81000544, 81171209, 81371406), the Shandong Provincial Natural Science Foundation, China (ZR2010HQ004, ZR2011HZ001), and the Shandong Provincial Outstanding Medical Academic Professional Program.

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China

    Lin Tan, Jin-Tai Yu & Lan Tan

  2. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

    Lin Tan, Jin-Tai Yu & Lan Tan

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  1. Lin Tan
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Tan, L., Yu, JT. & Tan, L. Causes and Consequences of MicroRNA Dysregulation in Neurodegenerative Diseases. Mol Neurobiol 51, 1249–1262 (2015). https://doi.org/10.1007/s12035-014-8803-9

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