MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review

Abstract

Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells-all indicative of disease progression-before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Huntington's disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies.

Keywords: biomarkers; diagnostic tools; limitations; microRNA; nervous system; neurodegenerative diseases; protein post-translational modifications; therapeutic tools.

Figure 1

Types of biomarkers and their uses in different disease stages. Biomarkers can be categorized into two main types: exposure biomarkers and disease biomarkers. Exposure biomarkers are employed to predict the occurrence of a disease, while disease biomarkers are utilized for monitoring, screening, and diagnosing a disease. Moreover, predictive biomarkers can forecast an individual’s vulnerability to disease (Taj et al., 2020).

Figure 2

MicroRNA biosynthesis pathways. Adapted from Huang (2022) by biorender.com. For details, see (O’Carroll, D., et al., 2013; Maffioletti, E., et al., 2014).

Figure 3

Alpha (α), beta (β), gamma (γ)-secretase in APP processing. Adapted from Gandy S. (2005).