New research published today sheds important light on how the production of a key protein in the brain is controlled, which could pave the way for new treatments for a wide range of neurological conditions.
In a study part-funded by Parkinson's UK, researchers investigated a section of genetic material known as antisense long non-coding RNA (lncRNA), which helps fine-tune the production of the protein tau inside brain cells. This precision in tau regulation is crucial for smooth functioning of the nerve cells.
Understanding the mechanism which helps regulate tau production could be the key to developing better treatments for conditions including Parkinson's, Alzheimer's, corticobasal degeneration and progressive supranuclear palsy.
The team's findings, published in Nature, show that tau, along with other key proteins involved in brain function, are controlled by very similar lncRNAs. This insight could help scientists develop the ability to control the production of these proteins and in turn, the development of certain neurological conditions.
The international team comprised of researchers from University College London (UCL), the Francis Crick Institute, University of Trento, Italy and the Karolinska Institute in Stockholm, Sweden.
Tau plays a really vital role inside our brain cells. It helps to stabilize and maintain the cytoskeletal structures that allow different materials to be transported to where they are needed. We know that too much tau is detrimental - the excess, unused tau converts into toxic species that may be responsible for damaging cells and driving the spread and progression of disease. However, despite the fact that tau has been studied for more than three decades, until now we did not know how neuronal cells exactly control tau protein production.
Excitingly, we found that the lncRNA that controls tau is not unique. Other key proteins we know to be involved in neurological conditions, including alpha-synuclein in Parkinson's and beta-amyloid in Alzheimer's, could be controlled by very similar lncRNAs. This means we may have found the key to regulating the production of a whole range of proteins involved in brain function and the development of these devastating conditions."
Professor Rohan de Silva and Dr Roberto Simone, Lead Investigators, University College London
"It's early days but we hope that these exciting new insights will lead to the development of drugs that can keep tau and other proteins under control, and that these therapies could be life-changing for degenerative brain conditions that as yet, we cannot slow or stop."
Professor David Dexter, Associate Director of Research at Parkinson's UK, said:
"Tau is emerging as one of the key determinants of different rates of progression in Parkinson's so understanding how this protein is regulated may be vital to finding better treatments and a cure for Parkinson's.
"This important research provides fantastic new insights into how tau production is controlled inside brain cells, and presents an exciting new opportunity for developing therapies that target this. It's especially exciting to see that similar mechanisms may be involved in controlling the production of many other key proteins implicated in other neurological conditions, as it suggests strategies targeting these mechanisms could be effective across many conditions."
Simone, R., et al. (2021) MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration. Nature. doi.org/10.1038/s41586-021-03556-6.