The older we get, the more we suffer from debilitating conditions: a weak heart, stiff limbs, memory loss, you name it. One of the most distressing ailments of old age is undoubtedly Alzheimer’s disease. The exact cause of this brain disease that leads to dementia is still unknown. But it is clear that there is a connection with malformed proteins or proteins that multiply inside and outside of brain cells and form harmful clots.
This process, also called protein aggregation, can also be the cause of Parkinson’s and other neurological diseases. This prompted researchers at the German University of Tübingen to look for ways to inhibit the secretion of harmful proteins outside of the cell. And they have managed to do so under the leadership of Della David.
First of all, the research – published yesterday in the journal Nature – has confirmed that keeping proteins in body fluids in good condition helps to counter both the aging process and infections.
David: “Decades of research have focused on protein quality control mechanisms inside the cell which work to avoid harmful protein aggregation. But such misfolded deposits also occur outside of cells.”
Misfolded amino acid chains
The body uses proteins as building blocks in cells, except that when formed as enzymes, for example, proteins are also responsible for a lot of metabolic processes and as such, also for transport through the body. To do this, the long chains of amino acids (which proteins are made up of) have to be folded in the correct three-dimensional form. And if that goes wrong, then that’s when the problems start.
In order to get an idea of protein formation outside of cells, the team around David came up with a new model using the minuscule roundworm caenorhabditis elegans, which is approximately 1 millimeter in length. David and her colleagues found 57 so-called extracellular regulators for protein aggregation in this roundworm.
In collaboration with Martin Haslbeck from the Technical University of Munich, David and her team identified the first extracellular regulator that binds to misfolded secreted proteins in the roundworms. David: “We knew that better protein quality control inside cells helps the animals to live longer. Now we have shown that better protein quality control outside the cell does that too.”
Proteins in humans and worms resemble each other
Co-author of the study, Ivan Gallotta, adds: “We were really surprised to find that animals with better extracellular protein quality control could survive over 30 percent longer during a pathogenic attack.”
According to the researchers, there are many similarities between the protein functions of humans and worms. In the study, human proteins were identified which had the greatest similarity with the worm’s extracellular regulators. David: “Our next goal is to determine if these regulators could be active against extracellular amyloid-beta protein aggregation, which is found in the brains of patients with Alzheimer’s disease.”
