Current Diagnostic Methods and Non-Coding RNAs as Possible Biomarkers in Huntington’s Disease

Abstract

Whether as a cause or a symptom, RNA transcription is recurrently altered in pathologic conditions. This is also true for non-coding RNAs, with regulatory functions in a variety of processes such as differentiation, cell identity and metabolism. In line with their increasingly recognized roles in cellular pathways, RNAs are also currently evaluated as possible disease biomarkers. They could be informative not only to follow disease progression and assess treatment efficacy in clinics, but also to aid in the development of new therapeutic approaches. This is especially important for neurological and genetic disorders, where the administration of appropriate treatment during the disease prodromal stage could significantly delay, if not halt, disease progression. In this review we focus on the current status of biomarkers in Huntington’s Disease (HD), a fatal hereditary and degenerative disease condition. First, we revise the sources and type of wet biomarkers currently in use. Then, we explore the feasibility of different RNA types (miRNA, ncRNA, circRNA) as possible biomarker candidates, discussing potential advantages, disadvantages, sources of origin and the ongoing investigations on this topic.

Beyond CAG Repeats: The Multifaceted Role of Genetics in Huntington Disease

“…For instance, a reduction in histone acetylation and in specific loci has been documented in several HD models and human HD biosamples [ 24 ]. In addition, there is also evidence that many RNA species can contribute to HD pathogenesis which has been described elsewhere [ 139 , 140 ]. One of these species, i.e., lncRNAs, RNA molecules exceeding 200 nucleotides in length, have been observed to exhibit notably higher expression in the brain, playing intricate roles in a multitude of cellular processes, including functions pertaining to transcriptional regulation and chromatin modulation.…”

Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases

“…Huntington’s disease is an autosomal dominant genetic disorder, and is a neurodegenerative disease [ 60 , 61 , 62 , 63 ]. The incidence of this disease varies greatly and depends on ethnicity [ 60 , 61 ].…”

“…Currently, HD is monitored using the Huntington’s Disease Rating Scale (UHDRS). The UHDRS is based on the determination of motor, cognitive, and behavioral abnormalities and functional capacity, which is accomplished by observing clinical symptoms [ 63 ]. Due to the subjective nature of determining disease progression, it is important to develop specific markers to help determine the progression of the disease [ 60 , 63 ].…”