International research done on mice and cells also found that this material is part of a larger family of non-coding genes * that contain other similar brain proteins such as beta-amyloid, which is associated with Alzheimer’s, and alpha-synuclein, which Involved in Parkinson’s Disease, Control and Regulate and Lewy Body Dementia.
Researchers say the groundbreaking results published in Nature shed important new light on how proteins associated with neurological diseases are made and controlled, and could pave the way for new treatments for a wide range of dementias.
The lead author, Dr. Roberto Simone (UCL Queen Square Institute of Neurology) said, “Tau plays an important role in our brain cells: it helps stabilize and maintain the cytoskeletal structures that allow various materials to be transported to where they are needed. We know that too much tau is harmful – the excess unused tau turns into toxic species that may be responsible for cellular damage and the spread and progression of degenerative diseases. Despite the fact that tau has been studied for more than three decades, we did not yet know how tau protein production was controlled. “
For the laboratory-based study, the researchers identified a section of the genetic material known as “Antisense Long Non-Coding RNA” (lncRNA). They discovered that this material does not produce tau directly, but rather helps regulate, optimize and suppress the production of the protein in brain cells. This precision offered by antisense lncRNA in tau regulation could be decisive for the smooth functioning of the nerve cells of the brain.
Excitingly, we found that the lncRNA that controls tau is not unique. Other key proteins that we know to be implicated in neurological diseases, including alpha-synuclein in Parkinson’s and beta-amyloid in Alzheimer’s, are controlled by very similar lncRNAs. This means that we may have found the key to regulating the production of a whole host of proteins involved in brain function and developing these devastating conditions. It’s early days, but we hope that these exciting new discoveries will lead to the development of drugs that can control tau and other proteins, and that these therapies can be used for degenerative diseases of the brain for which no treatment is yet available. could be life changing, let alone slow its progression.
Head of the research group, Professor Rohan de Silva
Other neurological conditions associated with tau protein include corticobasal degeneration and progressive supranuclear palsy.
Targeting dew to create new treatments
Previous genetic studies have shown that people with a certain form of the tau gene – called H1 – are more likely to have Parkinson’s, corticobasal degeneration, and progressive supranuclear palsy. We know that people with the H1 form of the gene produce more tau. We also know that the lncRNA we have identified helps limit tau production and that post mortem brain tissue studies show that this lncRNA may be reduced in people with Parkinson’s disease. So if we can find a way to increase levels of this lncRNA, we may be able to reduce the production of tau protein, which could help slow or stop damage to cells in the brain. That’s exactly what we’re working on right now. In particular, we are developing gene therapy to deliver this lncRNA to brain cells, and we are currently testing whether this approach can lower tau levels in mice and other animal models. If successful, we hope to advance this approach and develop it as a new therapy that can one day be tested in humans.
Professor de Silva
This important research offers fantastic new insights into the control of tau production in brain cells and offers an exciting new opportunity for the development of therapies that target it. It is particularly exciting to see that similar mechanisms may be involved in controlling the production of many other key proteins involved in other neurological conditions, as this suggests that strategies targeting these mechanisms are effective under many conditions could be.
Professor David Dexter, Assistant Director of Research at Parkinson’s in the UK
This research included collaborations within UCL and with research groups at the Francis Crick Institute, the UK Dementia Research Institute, St. George’s University in London, the Karolinska Institute in Sweden and the University of Trento in Italy.
Funding for this study was provided by the Reta Lila Weston Trust, Wellcome Trust, Medical Research Council (MRC), Parkinson’s in the UK, CBD Solutions, the PSP Association and CurePSP.
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* Non-coding DNA: Our genome contains coding genes, which are parts of our DNA that contain instructions for making proteins, the building blocks of our bodies. However, these coding genes make up only a small part of our genome – only 3% of the 3 billion letters (the nucleotides) of our genetic material. Until recently, the rest of the genome (non-coding) was considered junk DNA with no known function. However, it is now clear that the DNA that lies between the coding genes is not only used for human evolution, but also for regulating the function of cells and influencing the way coding genes produce proteins is crucial.
