Researchers at McMaster University have discovered a previously unknown cell-protective function of a protein, which could open new avenues for the treatment of age-related diseases and lead to healthier aging overall.
The team has discovered that a class of protective proteins known as MANF plays a role in the process that keeps cells efficient and functioning well.
The findings appear in the journal. Proceedings of the National Academy of Sciences.
Our cells make proteins and discard them after doing their job. This continuous and efficient maintenance process is known as cellular homeostasis. However, as we age, our cells’ ability to keep up decreases.
Cells can create proteins incorrectly and the cleanup process can become flawed or overwhelmed. As a result, proteins can clump together, leading to a harmful buildup that has been linked to diseases such as Alzheimer’s and Parkinson’s.
“If the cells are experiencing stress because this protein aggregation has started, the endoplasmic reticulum, which is where the proteins are produced and then released, receives the signal to stop producing them,” explains biology professor Bhagwati Gupta, who supervised the investigation.
“If the problem cannot be corrected, the cell will die, which ultimately leads to the degeneration of neurons and then to the neurodegenerative diseases that we see.”
Previous studies, including one from McMaster, had shown that MANF protects against increased cellular stress. The team set out to understand how this happens by studying microscopic worms known as C. elegans. They created a system to manipulate the amount of MANF in C. elegans.
“We could literally see where MANF was expressed in the worms because they are translucent. We could see it in all the different tissues. Within these tissues, MANF was present in structures known as lysosomes that are associated with lifespan and protein aggregation.” said Shane Taylor, now a postdoctoral fellow at the University of British Columbia who worked on his PhD project while at McMaster.
The team discovered that MANF plays a key role in the cell elimination process by helping to break down built-up proteins, keeping cells healthier and tidier.
Increasing MANF levels also activates a natural cleansing system within cells, helping them function better for longer.
“Although our research focused on worms, the findings reveal universal processes. MANF is present in all animals, including humans. We are learning fundamental, mechanistic details that could then be tested in higher systems,” Taylor said.
To develop MANF as a potential therapy, researchers want to understand what other actors MANF interacts with.
“The discovery of MANF’s role in cellular homeostasis suggests that it could be used to develop treatments for diseases that affect the brain and other parts of the body by targeting cellular processes, removing these toxic buildups in cells, and maintaining their health,” he said. Gupta.
“The whole idea of aging research is basically whether we can make processes better and more efficient. By understanding how MANF works and focusing on its function, we could develop new treatments for age-related diseases. We want to live longer and healthier. These types of players could help.