A research team, led by Indian-origin scientist Bhagwati Gupta, has made a groundbreaking discovery, identifying a novel protein function with therapeutic potential for age-related diseases.
Researchers at McMaster University in Canada have identified a previously unknown cell-protective function of a protein, holding promise for innovative therapies to combat age-related diseases and promote healthy aging.
A study published in Proceedings of the National Academy of Sciences shows cells' faulty protein production and cleanup can lead to harmful clumping, causing proteins to aggregate and accumulate, contributing to neurodegenerative diseases like Alzheimer's and Parkinson's.
When cells are stressed due to protein aggregation, the endoplasmic reticulum receives a signal to cease protein synthesis.Bhagwati Gupta, Biology Professor, McMaster University in Canada
“When cells are stressed due to protein aggregation, the endoplasmic reticulum receives a signal to cease protein synthesis,” said Professor Bhagwati Gupta, who oversaw the research.
MANF (Mesencephalic Astrocyte-Derived Neurotrophic Factor): A Neuroprotective Protein
The research team discovered that MANF, a class of neuroprotective proteins, plays a crucial role in maintaining cellular homeostasis and efficiency. This finding supports and extends previous research demonstrating MANF's protective effects against cellular stress.
Seeking to understand MANF's role in cellular homeostasis, Gupta's team employed C. elegans (Caenorhabditis elegans), a microscopic worm, as a model organism. They then developed a system to manipulate MANF levels, enabling a detailed analysis of its functional effects.
The study revealed that MANF plays a crucial role in cellular proteostasis by enhancing protein degradation. This process maintains cellular health and homeostasis. Notably, increased MANF levels activate a natural cellular clean-up mechanism, promoting longevity and efficiency.
Global significance:
“Although our investigation utilized a worm model, the findings have far-reaching implications, as MANF is conserved across animals, including humans." Our research elucidates fundamental and mechanistic details, providing a foundation for future studies in more complex systems, noted Shane Taylor, post-doctoral fellow at the University of British Columbia.
Although our investigation utilized a worm model, the findings have far-reaching implications, as MANF is conserved across animals, including humans.Shane Taylor, Post-doctoral fellow, University of British Columbia
Innovative age-related disease treatments:
This study paves the way for utilizing MANF as a potential therapeutic agent against age-related diseases. Further research will investigate MANF's interactions with other cellular mechanisms. As Gupta noted, "MANF's role in maintaining cellular homeostasis presents opportunities for developing treatments targeting neurodegenerative diseases and other conditions through modulation of toxic protein clearance pathways."
This groundbreaking discovery has the potential to yield innovative therapies promoting healthy aging and mitigating the risk of severe age-related diseases.
Reference:
Shane K. B. Taylor, Jessica H. Hartman, Bhagwati P. Gupta. The neurotrophic factor MANF regulates autophagy and lysosome function to promote proteostasis in Caenorhabditis elegans. Proceedings of the National Academy of Sciences, 2024; 121 (43) DOI: 10.1073/pnas.2403906121
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(Rehash/Sai Sindhuja K/MSM)