MiR-124 and the Underlying Therapeutic Promise of Neurodegenerative Disorders

Abstract

Neurodegenerative disorders (NDDs) are a group of chronic progressive neurological diseases based on primary neurodegeneration. The common pathological characteristics of various NDDs are neuronal degeneration, deletion, glial cell proliferation, and hypertrophy at specific locations in the nervous system. Proliferation and hypertrophy of microglia are manifestations of inflammation. MicroRNAs (miRNAs) have emerged as pivotal regulators of glial cells. MiRNAs are small non-coding molecules that regulate gene expression. Altered expression of miRNAs has been associated with several NDD pathological processes, among which regulation of the inflammatory response is key and a research hotspot at present. At the same time, miRNAs are also biological markers for diagnosis and potential targets for treating NDDs. MiR-124 is highly conserved and enriched in the mammalian brain. Emerging studies have suggested that miR-124 is closely related to the pathogenesis of NDDs and may be an effective treatment strategy to reduce inflammation associated with NDDs. In this review, we describe a summary of general miRNA biology, implications in pathophysiology, the potential roles of miR-124 associated with inflammation, and the use of miRNA as a future biomarker and an application for NDD therapy.

Overexpression of miR-124 in Motor Neurons Plays a Key Role in ALS Pathological Processes

“…Despite the critical role of miR-124 in neuronal differentiation and neurite outgrowth [ 30 ], its increased levels were associated with pathological events in neurodegenerative diseases, including ALS [ 24 , 31 ]. We have previously demonstrated that miR-124 is upregulated in NSC-34 mSOD1 MNs [ 25 ].…”

“…Its decrease was shown to attenuate NO production, while its upregulation was highlighted as increasing the risk of hypoxic injury and angiogenesis decrease, or even to be protective in SC injury [ 56 , 57 ]. In addition, miR-124 dysregulation was linked to the development of neurodegenerative disorders [ 31 ] and to several immune-system related pathways [ 58 ]. On the other hand, potential benefits of miR-124 upregulation were referred in Alzheimer’s disease through negative regulation of BACE1 expression [ 59 ].…”

MicroRNAs and target genes in epileptogenesis

“…miR‐124 plays key regulatory roles in neurological disease, 20 and its expression is decreased in patients with epilepsy 21 ; however, Brennan et al reported that increased miR‐124 does not alter epileptogenesis during the chronic phase of a kainic acid–induced epileptic rat model 22 . Further mechanistic analyses expounded on the reasons why miR‐124 does not influence spontaneous recurrent seizures; miR‐124 not only prevents hippocampal neuron restrictive silencing factor (NRSF) upregulation but also promotes the activation of hippocampal microglia and inflammatory cytokines 22 .…”

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

“…They play an important role in cell fate determination, cell differentiation, organ development, and physiology and are also involved in various pathologies in humans (Almeida et al, 2011 ; Desvignes et al, 2015 ). miRNAs regulate target gene mRNA mainly by cutting off the target gene’s RNA molecule, thereby inhibiting target gene translation and inhibiting recombination (Han et al, 2019 ). By binding to the RNA-induced silencing complex, the nucleotide sequence of miRNA allows targeted base pairing with the 3′-untranslated region of complementary mRNA.…”