by Unusual forms of RNA associated with the formation of solid aggregates in the brains of Amyotrophic Lateral Sclerosis (ALS) patients could pave the way for new treatment options, according to a study conducted by researchers at Imperial College London. ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease characterized by the degeneration of nerve cells in the spinal cord and brain. Currently, there are no known cures for ALS or other neurodegenerative diseases such as dementia and Alzheimer’s, which are the leading cause of death in the UK.
The formation of these solid aggregates, or protein clumps, in the brain has long been considered a hallmark of neurodegenerative diseases. Therefore, many drugs have been developed to break down these protein aggregates. However, none of these drugs have shown significant improvements in symptom management. Therefore, the research team led by Dr. Marco Di Antonio at Imperial College London explored an alternative mechanism that could contribute to aggregate formation in ALS.
The study, published in Nature Communications, suggests that unconventional forms of RNA could play a crucial role in the build-up of these aggregates. The team focused on investigating the gene C9orf72, which is mutated in some ALS cases. This gene contains a repeat expansion, which is converted into RNA when the DNA is read. By studying the behavior of the C9orf72 RNA, the researchers discovered that ALS-related RNA expansions can generate a unique structure known as multimolecular G-quadruplex (mG4). These mG4 structures form a network that leads to the formation of solid aggregates.
The researchers demonstrated that proteins were more likely to aggregate in the presence of mG4 networks. Additionally, they found that preventing the formation of mG4 structures resulted in the prevention of RNA condensation and protein aggregation. To further validate their findings, the team also observed accumulations of mG4s within aggregates in the spinal motor neurons of ALS patients.
Dr. Marco Di Antonio emphasized that while their findings are not the definitive answer to the puzzle of neurodegenerative diseases, they provide valuable insights into alternative pathways for aggregate formation. This discovery opens up the possibility of developing new therapies targeting the disruption of mG4s and other unconventional RNA structures. Moreover, the team believes that similar strategies could also be effective in treating other neurodegenerative diseases.
Moving forward, the researchers plan to investigate the association between mG4s and protein aggregates in more complex cellular environments to gain a better understanding of the processes involved. These further studies will shed light on whether disrupting mG4 aggregation could provide a viable therapeutic pathway for the treatment of ALS and other related conditions.
The search for effective treatments for neurodegenerative diseases is of utmost importance, considering the lack of current options. Targeting unconventional RNA structures, such as mG4s, holds great potential to address the underlying causes of these debilitating conditions and pave the way for novel therapeutic interventions.
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
Money Singh is a seasoned content writer with over four years of experience in the market research sector. Her expertise spans various industries, including food and beverages, biotechnology, chemical and materials, defense and aerospace, consumer goods, etc.
