A protein normally involved in cleaning cells could, in the event of dysfunction, clump together into fibrils and be the cause of neurodegenerative diseases such as Alzheimer’s.
- First cause of dementia in the world with 60 to 70% of cases, Alzheimer’s disease affects approximately 900,000 people in France.
- 8% of French people over 65 will be affected by 2020.
- It is estimated that 225,000 new cases are diagnosed each year in France.
Is the TMEM106B protein, like the tau protein and amyloid plaques, involved in the development of Alzheimer’s disease, but also in that of other neurodegenerative diseases?
This is the conclusion of a new study conducted by an international team of 22 collaborators and published in the journal Cell. This TMEM106B protein normally serves to clean up molecular debris in cells. But in the event of a malfunction, it would clump together into fibrils, which would hinder the proper functioning of the cells. Each neurodegenerative disease would also have its own signature in terms of tangled proteins, as explained by Dr. Anthony Fitzpatrick, principal investigator at the Zuckerman Institute in Columbia (USA): “These disease-associated proteins have their own unique shapes and behaviors.”
Fibrils observed for the first time
Researchers have long been interested in the proteins responsible for the formation of tangles as targets for new drugs. But until now, the behavior of the TMEM106B protein in fibrils had not been observed.
TMEM106B is known to clean out waste that builds up in our cells as we age. But it can happen that the TMEM106B molecules split into fragments, which self-assemble and can form fibrils that clog the cells.
To make this discovery, the researchers first extracted proteins from brain tissue of 11 patients who died of three neurodegenerative diseases associated with protein tangles: progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB) and frontotemporal lobar degeneration (FTLD).
Using a high-powered microscope, the team took snapshots of protein molecules, from which they then built three-dimensional models, including those of the TMEM106B protein.
A possible new cause of neurodegenerative diseases
They then found that this protein created many fibrils and that these were not only present in the brain tissue of patients, but also that they could be the cause of neurodegenerative diseases. According to the authors, this tangle formation of TMEM106B could kill brain cells, leading to dementia, movement problems, speech pathologies and other symptoms of Alzheimer’s disease, PSP, FTLD and other brain diseases with telltale protein tangles.
“We now have a promising new lead, emphasizes Dr. Fitzpatrick. It could point to a common thread linking a series of neurodegenerative diseases and open the way to new interventions.”
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