Repressor Element-1 Binding Transcription Factor (REST) as a Possible Epigenetic Regulator of Neurodegeneration and MicroRNA-Based Therapeutic Strategies

Abstract

Neurodegenerative disorders (NDD) have grabbed significant scientific consideration due to their fast increase in prevalence worldwide. The specific pathophysiology of the disease and the amazing changes in the brain that take place as it advances are still the top issues of contemporary research. Transcription factors play a decisive role in integrating various signal transduction pathways to ensure homeostasis. Disruptions in the regulation of transcription can result in various pathologies, including NDD. Numerous microRNAs and epigenetic transcription factors have emerged as candidates for determining the precise etiology of NDD. Consequently, understanding by what means transcription factors are regulated and how the deregulation of transcription factors contributes to neurological dysfunction is important to the therapeutic targeting of pathways that they modulate. RE1-silencing transcription factor (REST) also named neuron-restrictive silencer factor (NRSF) has been studied in the pathophysiology of NDD. REST was realized to be a part of a neuroprotective element with the ability to be tuned and influenced by numerous microRNAs, such as microRNAs 124, 132, and 9 implicated in NDD. This article looks at the role of REST and the influence of various microRNAs in controlling REST function in the progression of Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) disease. Furthermore, to therapeutically exploit the possibility of targeting various microRNAs, we bring forth an overview of drug-delivery systems to modulate the microRNAs regulating REST in NDD. Graphical abstract

Recognizing Alzheimer's disease from perspective of oligodendrocytes: Phenomena or pathogenesis?

“…138 response. [143][144][145] By contrast, we found that there are only a few research reports on the involvement of miRNAs in the differentiation and maturation of OLs in AD. 146,147 How miRNAs regulate factors of OLs differentiation and maturation in AD is worth further exploration.…”

Epigenetic Alterations in Alzheimer’s Disease: Impact on Insulin Signaling and Advanced Drug Delivery Systems

“…Looking into the cellular level changes in an AD brain, various molecular pathways and intracellular signaling are dysregulated, which include Aβ and tau, inflammatory-immune responses, homeostasis and plasticity of synapses, and oxidative stress and their dysregulation results from genetic, environmental, and biologic interventions [ 17 , 18 ]. Furthermore, accumulating evidence has been pointing towards the possibility of an imbalance in epigenetic mechanisms responsible for abnormal synaptic plasticity and memory-associated genes in AD [ 19 , 20 , 21 , 22 , 23 ].…”