Take a tour of the deep cell of Alzheimer’s disease, and you will find a small fraction of the protein that is marked. Since the 1980s, when neuroscientists first discovered these proteins, researchers have discovered that other neurotransmitters have their own set of proteins.
“Each of these diseases has a specific type of protein, or fibril, associated with it,” said Anthony Fitzpatrick, Ph.D., chief research officer at the Zuckerman Institute in Columbia. “These disease-related proteins have their own characteristics and characteristics,” said Dr. Fitzpatrick, an assistant professor of biology at Irving Columbia University Medical Center and a member of the Columbia Taub Institute for Research on Alzheimer’s Disease and Aging Brain Specialists. .
Published today at CellResearch by Drs. Fitzpatrick and an international team of 22 collaborators show a new fibril in the brains of patients, whose protein is produced by cell cleansing.
“We have a dramatic effect and the stimulus we hope will have an impact on the management of neurodegenerative diseases,” said Andrew Chang, the first author of the paper in the Fitzpatrick laboratory. Drug researchers have long pursued proteins that cause tangle as the target of new drugs, but this search so far has yielded disappointing results.
Fibril-related diseases, some common and some rare, together they affect millions of people around the world. Occurrence is increasing as the population increases and people live longer. Misunderstanding what is going on in these neurodegenerative diseases has a personal face for Dr. Fitzpatrick: Losing an uncle to one of them, development of pneumonia (PSP).
“We have found that a protein called TMEM106B can cause fibrils, and this behavior has not been known before,” said Xinyu Xiang, a former member of the Fitzpatrick laboratory at the Zuckerman Institute, and in is now a graduate student at Stanford University’s Department of Biology. “This protein is essentially a component of lysosomes and endosomes, which are the cells that cleanse the lining that develops in our cells as we grow.”
Normally, TMEM106B cells invade the membranes of waste control cells. In a sleuthing model of the laboratory, the Fitzpatrick team discovered that TMEM106B cells could split in two. Organic fibers may be involved in what researchers suspect may be co-fibrils.
To do this research, researchers began extracting proteins from brain tissue contributed to 11 patients who died from three neurodegenerative diseases that were associated with non-specific proteins: PSP, dementia with Lewy body (DLB) and frontal lobe degeneration (FTLD). FTLD is the most common type of dementia for those under 60 years of age.
“It is interesting to note that the only way we can do this research is because of the people who have contributed to their brain,” said Marija Simjanoska, first author and one of three students working on work.
Co-author Ian Mackenzie, MD, of the University of British Columbia, and co-authors Dennis Dickson, MD, and Leonard Pertrocelli, Ph.D., of the Mayo Clinic in Florida, contributed to the discovery of this valuable research resource. Join Drs. Fitzpatrick and Mackenzie as co-authors on paper are Michael Stowell, Ph.D., of the University of Colorado, Boulder. The team consists of 23 research researchers from several other institutions, including three in Belgium.
With the global cryogenic electron microscope (cryo-EM), the team took pictures of single protein molecules at different angles. From these, the researchers constructed three major proteins in detail. These models, in turn, helped researchers identify TMEM106B by predicting knowledge about the exact sequence of amino-acid protein blocks. Much like the letters binding together specific words, different amino-acid molecules are built into proteins, each with its own shape and function.
The researchers speculated that one of the most well-known proteins that produce fibril, such as tau protein in Alzheimer’s disease, would end up being the same product from cryo-EM data. Alternatively, adaptive exercise, which includes research in a large body of protein sequences, yields a reversible effect.
The researchers found that the unique protein matched the 135-amino-acid fraction of TMEM106B. This is an interesting revelation because this protein is discovered more than a decade ago in the hunt for large genes associated with FTLD.
To date, handouts have only shown that TMEM106B fibrils are present in diseased brain cells, not that fibrils cause disease. Once again, Drs. Fitzpatrick points out, the number of TMEM106B fibrils in tissues from different. brain diseasescombined with the normal location of proteins in lysosomes and endosomes, suggests the potential for pathogenesis.
In them Cell paper, the researchers speculated that the formation of TMEM106B fibrils disrupts the function of the lysosome, which, in turn, promotes the production of fibrils produced by other well-known fibrillar proteins. These disorders can kill brain cells, causing dementia, movement problems, speech disorders and other symptoms of Alzheimer’s, PSP, FTLD and other brain disorders along with reporting. protein tangles.
“We now have an exciting new leader,” said Dr. Fitzpatrick. “It can point to a common thread that connects the range neurodegenerative diseases and could pave the way for new interventions. ”
Andrew Chang et al, Homotypic fibrillization of TMEM106B across various neurodegenerative diseases, Cell (2022). DOI: 10.1016 / j.cell.2022.02.026
hintStudies show potential link between multiple neurodegenerative diseases (2022, March 4) recovered 4 March 2022 from https://medicalxpress.com/news/2022-03-common-thread-neurodegenerative-diseases.html
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