Imagine you’re about to eat a big pizza. In order to not choke on it, you cut it up into slices and eat it bite by bite. And while you’re chomping down on your slices, cells inside your body are busy slicing the built-up protein clumps into pieces that are more manageable for the body’s trash system –otherwise it would clog up and malfunction. 

Researchers from the department of Biomedicine at Aarhus University have just released a new study, which for the first time documents exactly how those clumps of unwanted protein get reduced to smaller pieces before being disposed of by the cells’ garbage disposal system – called autophagy.

The process involves something called the proteasomal 19S subunit and DNAJB6-HSP70-HSP110 module, which together practically form a grinder. And while that may sound more like a barcode on a printer, it is actually a very important key that may lead to better treatments of diseases like characterized Alzheimer’s, Parkison’s, Huntington’s, ALS and other diseases that are characterized by the accumulation of clumps, in most cases formed  by a specific protein, says Professor Fulvio Reggiori who’s behind the study. 

“We knew that cells are packing proteins and other cellular material into clump, the aggregates, to be discarded in the major disposal center of the cell, the lysosomes. But we do not still know exactly how they are discarded. Now we discovered that those clumps must be reduced is size through something that could be seen as a piecemeal. The how is important, because it can help us find ways to treat some of the diseases that develop when our cells start to accumulate protein clumps and other debris because of mutations or other causes, something that occurs in neurodegenerative diseases such as Alzheimer’s, Parkison’s, Huntington’s, ALS and many other pathologies, also affecting other organs.”

And while the discovery is not a cure, it is a step closer, says Fulvio Reggiori:

“We know that augmenting autophagy, which is one of the two major cleaning systems in our cells, can delay the onset of several of the devastating neurodegenerative diseases mentioned. Our findings suggest that a combined treatment where we enhance both the breaking down of the big protein clumps into smaller pieces to make them a better substrate for autophagy and autophagy, may be a much better therapeutic approach for these diseases.”

The researcher’s will now focus their research on exactly the identified machine breaks the clumps, and whether any additional players within the cells play a part in this, says Fulvio Reggiori. 

“We are just starting to decipher the mechanism of this whole cell-cleaning process, and we need to deep dive into the details before we can start to work on actual treatments, but understanding how we can enhance it, will certainly help to eliminate, at least partially, those toxic protein aggregates leading to the above-mentioned lethal neurodegenerative diseases.”

The research more information: 

 Study type: Basic/fundamental research
Collaborators:
AU: Muriel Mari, Biomedicine, AU
Abroad:
Mario Mauthe, Mark Hipp and Harm Kampinga, University Medical Center Gronigen, NL
Lukas Kapitein, Utrecht University, NL
Sabine Schipper-Krom, Academic Medical Center Amsterdam, NL
Anne Simonsen, University of Oslo, N
External funding: Novo Nordisk Foundation (NNF), Lundbeck Foundation, Dutch research Council (NWO) and Swiss National Found (SNF)
Information on any impartiality issues: None
Read more in the scientific paper: https://www.nature.com/articles/s41556-025-01747-1

Contact:
Professor Fulvio Reggiori
Aarhus Universitet, Health,Department of Biomedicine
Phone: +4587159527
E-mail: f.m.reggiori@biomed.au.dk