It’s already known that protein ‘clumps’ can cause a variety of neurodegenerative diseases, from Alzheimer’s to Parkinson’s, but now researchers believe that they’ve identified how our cells protect themselves from these clumps.
The study, carried out by a team from the University of Glasgow in collaboration with University of Dundee, involved compressing neurons inside a 3-D culture while continuously monitoring changes in the structure of the cell via a powerful microscope. A custom-built device was used for the process to give the scientists an insight into the role of a specific gene known as UBQLN2. It also enabled them to see how it helps the cells to remove clumps of toxic protein from the body and thus protect it from disease.
By using a combination of mouse models of Huntington’s, cell biology and biochemistry, the team were able to see that the main function of this gene is to assist the cell in removing the dangerous clumps of protein. To do this, the gene detangles the clumps before shredding them so that future tangles are prevented. In the mouse models it was seen that when the UBQLN2 gene mutated it was no longer able to help the cells to remove the protein clumps.
While protein clumps are a natural part of the aging process and are usually dealt with by UBQLN2, if the gene mutates or becomes faulty it’s unable to perform its function. This leads to degeneration of the neurons and ultimately to neurodegenerative diseases, such as Parkinson’s, Huntington’s disease and Alzheimer’s. These patients exhibit clear clumps of amyloid proteins within their brains.
In previous studies, it’s been shown that this gene, when faulty, leads to ALS with Frontotemporal Dementia, although it wasn’t known why this happened. This current study has enabled scientists to more fully understand this mechanism and why its mutation is so damaging to the body. Now they hope that their findings will go some way to helping find new treatments for patients with neurodegenerative diseases.
The study was published in a recent edition of the online journal Cell.