A University of California, Irvine-led research team has made a significant breakthrough in understanding the molecular mechanisms driving Huntington’s disease (HD), a neurodegenerative disorder characterized by RNA processing defects. The study, published online in Nature Neuroscience, reveals intricate connections between two key regulators of RNA processing and identifies potential therapeutic targets for treating HD and other related diseases.
Researchers discovered that mutations in the gene responsible for HD disrupt normal RNA processing mechanisms, leading to abnormal splicing errors. They found that binding of specific proteins and chemical tags alters the regulation of genes involved in HD, highlighting a complex interplay between cellular functions.
The team used advanced genomic and molecular biology techniques to explore how m6A RNA modifications direct TDP-43 protein to regulate crucial RNAs. Their study sheds light on a critical process essential for accurate RNA splicing, which is compromised in HD patients.
By targeting key processes like RNA splicing and modification, researchers may develop new treatments for neurodegenerative diseases more broadly. This breakthrough has far-reaching implications for the treatment of Huntington’s disease, amyotrophic lateral sclerosis (ALS), frontotemporal lobar dementia (FTLD), and Alzheimer’s disease, where TDP-43 dysregulation is significant.
The study was a collaborative effort involving researchers from UC Irvine, Harvard University, the Massachusetts Institute of Technology, Columbia University, and Ionis Pharmaceuticals. Funding for the research came from various sources, including the Chan Zuckerberg Initiative’s Collaborative Pairs awards program and National Institutes of Health grants.
Source: https://news.uci.edu/2025/01/08/uc-irvine-led-team-discovers-potential-new-therapeutic-targets-for-huntingtons-disease