New Delhi: Researchers at McMaster University have identified a previously unknown cell-protecting role of the protein MANF, offering potential new treatments for age-related diseases like Alzheimer’s and Parkinson’s. The findings, published in the Proceedings of the National Academy of Sciences, could improve cellular health and promote healthier aging.
The study, led by biology professor Dr Bhagwati Gupta, revealed that the protein MANF plays a crucial role in maintaining cellular homeostasis. This process ensures that proteins are made correctly, perform their functions, and are then discarded.
However, as aging progresses, cells struggle to manage this process, leading to harmful protein buildup. “If the cells are experiencing stress because this protein aggregation has started, the endoplasmic reticulum, which is where proteins are made and then released, gets the signal to stop making these proteins,” explains Dr Gupta. “If it can’t correct the problem, the cell will die, which ultimately leads to degeneration of the neurons and then neurodegenerative diseases that we see.”
To study MANF's role, researchers used the microscopic worm C. elegans, manipulating its MANF levels. Shane Taylor, a post-doctoral fellow at the University of British Columbia who worked on this project during his PhD at McMaster, said, “We could literally see where MANF was expressed in the worms because they are translucent. We could see it in all different tissues. Within these tissues, MANF was present in structures known as lysosomes, which are associated with lifespan and protein aggregation.”
The study found that MANF is involved in the cell's clean-up process, helping break down accumulated proteins and keep cells healthier. Increasing MANF levels also activated a natural clean-up system, improving cellular function over time.
“Although our research focused on worms, the findings uncover universal processes. MANF is present in all animals, including humans. We are learning fundamental and mechanistic details that could then be tested in higher systems,” Taylor noted.
The researchers aim to explore how MANF interacts with other cellular components, with the goal of developing it as a therapeutic approach.
“Discovering 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, clearing out these toxic clumps in cells and maintaining their health,” said Dr Gupta.
Dr Gupta also emphasized, “The central idea of aging research is basically can we make the processes better and more efficient. By understanding how MANF works and targeting its function, we could develop new treatments for age-related diseases. We want to live longer and healthier. These kinds of players could help that.”