“Common thread, silver bullet, naïve hope?” (Dr. Golbe’s musings)

Dr. Larry Golbe, a world-renowned expert on progressive supranuclear palsy (PSP), has his own blog (psp-blog.org) to which he occasionally publishes insights into the latest research.

In late March 2022, he published about two papers he read on the protein TMEM106B.  He says, “This stuff is known to be a component of healthy lysosomes and endosomes, components of the cell’s garbage disposal mechanism.”

[One paper] found that the brains of healthy elderly persons have abnormal aggregates of a misfolded form of the protein TMEM106B.  These abnormal aggregates were found “even more abundantly in a raft of neurodegenerative diseases: Alzheimer’s, CBD, multiple types of FTD, Parkinson’s, dementia with Lewy bodies, multiple system atrophy and multiple sclerosis.

The second paper (authors from Columbia University, Mayo Clinic Jacksonville, etc) “found the same TMEM106B aggregates” in those with PSP. 

Dr. Golbe says,  

An interesting finding is that unlike tau, TMEM106B misfolds the same way in all the diseases analyzed so far.  This may have huge potential implications: if (and this is a big “if”) the misfolded TMEM106B plays an important role in the formation of the misfolding and toxicity of tau and the other disease-specific proteins, and if (another big “if”) this misfolding is the rate-limiting step in the loss of brain cells in the neurodegenerative disorders, THEN preventing TMEM106B from forming or from misfolding, or targeting it with antibodies or drugs could be the silver bullet that prevents all of these diseases, PSP included.  That could be a naïve hope…

Read Dr. Golbe’s blog post here

“Common thread, silver bullet, naïve hope?”
Dr. Larry Golbe
March 16, 2022

Let’s hope!