The motor, cognitive, and psychological characteristics of Huntington disease (HD), an autosomal-dominant neurodegenerative disorder, are clearly shared. Typically establishing in maturity, the symptoms rise permanently over a period of 10 to 15 years (Ross and Tabrizi, 2011). George Huntington, an American physician, was the earliest to define it in 1872. He declared that a genomic disease that caused chorea and psychological problems competed in some families and that it was reflected “one of the incurables.” Sadly, some 150 years later, this is still the case. However, we now have a hard basis in the genetics and pathobiology of HD, which allows us to develop possible treatment approaches.(Ghosh & Tabrizi, 2018).
Increased expression levels of the restrictive element-1 silencing transcription factor (REST) has been witnessed in both mouse models of Huntington’s disease (HD) and human HD brain tissue (Buckley et al., 2010; Johnson and Buckley, 2009). REST is necessary in controlling neuronal genes and is broadly expressed all over the body, mainly in immature central nervous system (CNS) cells. It functions by suppressing many neuron-specific genes through the recruitment of a multi-subunit complex of DNA monitoring motifs called repressor 1 (Buckley et al., 2010). REST backings neuroprotection by downregulating genes involved in oxidative stress and amyloid toxicity and by modifying those related with synaptic plasticity and normal aging (Hwang and Zukin, 2018).
MicroRNAs targeting the REST complex can considerably decrease expression levels of various miRNAs, containing miR-330, miR-29a, miR-132, and miR-124 (Yoo et al., 2011). Notably, miR-132 and miR-124 are considerably decreased in HD (Johnson et al., 2008). miR-124 is mostly expressed in healthy neurons and targets a REST component gene (Lee et al., 2017). During CNS development, miR-124 controls synaptonemal complex protein 1 (SCPY1) levels by directing its 3′-UTR (Visvanathan et al., 2007). In addition, miR-132 downregulation stimulates axonal growth by stopping p250GA transcript in the cortex of HD patients (Fukuoka et al., 2018). REST upregulation in vivo alters the appearance of some miRNAs, including miR-9*, miR-9, and miR-124 (Bithell et al., 2009). In detail, miR-124 mainly prevents non-neuronal gene expression in neurons, which is vital for neuronal growth. miR-9 and miR-9* control REST levels, thus disturbing HD progression (Chang et al., 2017). These results recommend that REST can directly stops gene expression and ultimately effect miRNA functions and their target genes by changing the levels of some miRNAs. Additional miRNAs, such as miR-9, miR-142, miR-155, and miR-22, are also involved in neurodegenerative diseases, containing ischemic stroke, ischemia-reperfusion (IR) injury, and multiple sclerosis (MS).
