Investigating Neuron Degeneration in Huntington’s Disease Using RNA-Seq Based Transcriptome Study

Abstract

Huntington’s disease (HD) is a progressive neurodegenerative disorder caused due to a CAG repeat expansion in the huntingtin (HTT) gene. The primary symptoms of HD include motor dysfunction such as chorea, dystonia, and involuntary movements. The primary motor cortex (BA4) is the key brain region responsible for executing motor/movement activities. Investigating patient and control samples from the BA4 region will provide a deeper understanding of the genes responsible for neuron degeneration and help to identify potential markers. Previous studies have focused on overall differential gene expression and associated biological functions. In this study, we illustrate the relationship between variants and differentially expressed genes/transcripts. We identified variants and their associated genes along with the quantification of genes and transcripts. We also predicted the effect of variants on various regulatory activities and found that many variants are regulating gene expression. Variants affecting miRNA and its targets are also highlighted in our study. Co-expression network studies revealed the role of novel genes. Function interaction network analysis unveiled the importance of genes involved in vesicle-mediated transport. From this unified approach, we propose that genes expressed in immune cells are crucial for reducing neuron death in HD.

Mechanism and Therapeutic Prospect of miRNAs in Neurodegenerative Diseases

“…HD is caused by an increase in CAG trinucleotide duplication of the HTT, which leads to protein aggregation and leads to impaired motor and cognitive function in patients. Therefore, in the treatment of neurodegenerative disease such as HD, the noncoding characteristics of RNA and the interference technology of miRNAs are used to inhibit the expression of mutant HTT and other mutant proteins at the posttranscriptional level to improve the migration defect of immune cells [ 62 – 64 ].…”

How does the age of control individuals hinder the identification of target genes for Huntington’s disease?

“…With the advances in bioinformatics, these samples have undergone extensive reanalysis through various pipelines ( Seefelder and Kochanek, 2021 ; Sneha et al, 2023 ). Despite the commendable efforts invested in these studies, the differentially expressed genes (DEGs) identified so far have not yielded valuable pharmaceutical or prognostic targets conducive to HD drug development ( Labadorf et al, 2015 ; 2016 ; Lin et al, 2016 ; Agus et al, 2019 ; Seefelder and Kochanek, 2021 ; Sneha et al, 2023 ).…”