Non-Coding RNA in Microglia Activation and Neuroinflammation in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by complex pathophysiological features. Amyloid plaques resulting from extracellular amyloid deposition and neurofibrillary tangles formed by intracellular hyperphosphorylated tau accumulation serve as primary neuropathological criteria for AD diagnosis. The activation of microglia has been closely associated with these pathological manifestations. Non-coding RNA (ncRNA), a versatile molecule involved in various cellular functions such as genetic information storage and transport, as well as catalysis of biochemical reactions, plays a crucial role in microglial activation. This review aims to investigate the regulatory role of ncRNAs in protein expression by directly targeting genes, proteins, and interactions. Furthermore, it explores the ability of ncRNAs to modulate inflammatory pathways, influence the expression of inflammatory factors, and regulate microglia activation, all of which contribute to neuroinflammation and AD. However, there are still significant controversies surrounding microglial activation and polarization. The categorization into M1 and M2 phenotypes may oversimplify the intricate and multifaceted regulatory processes in microglial response to neuroinflammation. Limited research has been conducted on the role of ncRNAs in regulating microglial activation and inducing distinct polarization states in the context of neuroinflammation. Moreover, the regulatory mechanisms through which ncRNAs govern microglial function continue to be refined. The current understanding of ncRNA regulatory pathways involved in microglial activation remains incomplete and may be influenced by spatial, temporal, and tissue-specific factors. Therefore, further in-depth investigations are warranted. In conclusion, there are ongoing debates and uncertainties regarding the activation and polarization of microglial cells, particularly concerning the categorization into M1 and M2 phenotypes. The study of ncRNA regulation in microglial activation and polarization, as well as its mechanisms, is still in its early stages and requires further investigation. However, this review offers new insights and opportunities for therapeutic approaches in AD. The development of ncRNA-based drugs may hold promise as a new direction in AD treatment.

Plasma miR-203a-3p as a Novel Predictor of Dementia in Patients with Parkinson’s Disease

“…DJ-1 may protect neurons from cytotoxic oxidative damage in its physiological function [ 46 , 47 , 48 ]. The overexpression of miR-203a-3p has been suggested to cause a deficiency of DJ-1 and further result in oxidative-stress-induced cell death [ 46 , 47 ], microglia-regulated neuronal injury [ 49 ], and the promotion of the neurodegenerative phenotype in vivo [ 50 ]. The above findings suggest that miR-203a-3p might contribute to the underlying mechanism related to cognitive impairment in PD and support the hypothesis of selecting miR-203a-3p as a biomarker for the diagnosis of PDD.…”

A bibliometric and visual analysis of epigenetic research publications for Alzheimer’s disease (2013–2023)

“…ncRNAs are closely related to the epigenetic mechanisms of AD and are diverse. In this article, we focus on miRNAs and lncRNAs ( He et al, 2023 ). So far, many different miRNAs have been widely studied and linked with the development of AD, and the end result of the action of miRNAs has been the translational inhibition and/or degradation of targeted miRNAs ( Huntzinger and Izaurralde, 2011 ).…”

Plasma mir-203a-3p as a Novel Diagnostic Biomarker in Patients with Parkinson’s Disease Dementia

“…miR-203a-3p was suggested to binding to the 3'UTR of human DJ-1, which is a Parkinson's disease-related gene and may prevent neurons from cytotic oxidative damage [34][35][36]. The overexpressed miR-203a-3p was suggested to cause deficiency of DJ-1 and further result in the oxidative stress-induced cell death [34,35], the microglia-regulated neuronal injury [37] and promoted neurodegenerative phenotype in vivo [38]. MiR-203a-3p was also assumed to binding to the 3'UTR of SNCA, encoded for α-syn, which was well-known as elevating risk of developing PD [39,40].…”