Involvement of Astrocytes and microRNA Dysregulation in Neurodegenerative Diseases: From Pathogenesis to Therapeutic Potential

Abstract

Astrocytes are the most widely distributed and abundant glial cells in the central nervous system (CNS). Neurodegenerative diseases (NDDs) are a class of diseases with a slow onset, progressive progression, and poor prognosis. Common clinical NDDs include Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Although these diseases have different etiologies, they are all associated with neuronal loss and pathological dysfunction. Accumulating evidence indicates that neurotransmitters, neurotrophic factors, and toxic metabolites that are produced and released by activated astrocytes affect and regulate the function of neurons at the receptor, ion channel, antigen transfer, and gene transcription levels in the pathogenesis of NDDs. MicroRNAs (miRNAs) are a group of small non-coding RNAs that play a wide range of biological roles by regulating the transcription and post-transcriptional translation of target mRNAs to induce target gene expression and silencing. Recent studies have shown that miRNAs participate in the pathogenesis of NDDs by regulating astrocyte function through different mechanisms and may be potential targets for the treatment of NDDs. Here, we review studies of the role of astrocytes in the pathogenesis of NDDs and discuss possible mechanisms of miRNAs in the regulation of astrocyte function, suggesting that miRNAs may be targeted as a novel approach for the treatment of NDDs.

Roles of Micro Ribonucleic Acids in Astrocytes After Cerebral Stroke

“…Treatment for the targets of genes is the most efficient and accurate, and also provides the development of novel drugs. It has been proven that miRNAs have a relatively small molecular weight and they can readily pass the BBB and exhibit stable expression in peripheral blood ( Bai et al, 2021 ). Since the permeability of BBB will increase after stroke ( Abdullahi et al, 2018 ), the concentration of miRNAs in the blood may be used as an indicator that prompts stroke prognosis, and could also help predict the outcome of post-stroke rehabilitation ( Mirzaei et al, 2018 ).…”

Astrocyte Reprogramming in Stroke: Opportunities and Challenges

“…miRNAs play an important role in cell differentiation, organ development, and cell fate determination, and are also involved in various human pathologies ( Ha and Kim, 2014 ). Emerging studies have shown that many miRNAs are expressed in astrocytes, and some are involved in astrocyte differentiation, activation, and reprogramming activities ( Bai et al, 2021 ). As miR-9 and miR-124 control multiple genes regulating neuronal differentiation and function, Yoo et al (2011) proposed that these miRNAs might contribute to neuronal fates.…”

Astrocytic MicroRNA in Ageing, Inflammation, and Neurodegenerative Disease

“…Here, we review accumulating evidence implicating disrupted miRNA expression in astrocytes and ADEVs in the pathophysiology of neurodegenerative diseases, highlighting downstream targets of the perturbed miRNA and the biological pathways affected. We build on recent reviews ( Neal and Richardson, 2018 ; Bai et al, 2021 ) by considering alterations to astrocytic miRNA expression in ADEVs and that arising from ageing and inflammatory processes. It is important to note that studies utilising astrocytoma or glioblastoma cells to represent astrocytes were not included due to the well-documented differences in miRNA expression between primary astrocytes and cultures derived from astrocytoma cell lines ( Lee et al, 2013 ; Zhou et al, 2017 ).…”