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In the body, protein homeostasis is essential, bringing together all the mechanisms that guarantee the maintenance of protein balance in a cell. Disruption of this homeostasis can cause harmful protein aggregation, which can lead to neurodegenerative diseases such as Alzheimer’s or Parkinson’s. In a recent study, researchers revealed a potential protective function of a protein involved in this important process. This discovery opens the way to the development of promising therapeutic strategies against age-related neurodegenerative diseases.
Recently, scientists from the Center for Healthy Aging at the Department of Cellular and Molecular Medicine at the University of Copenhagen, led by Professor Lene Juel Rasmussen, identified the OSER1 protein as a potential regulator of aging and longevity. However, the precise mechanisms involving this protein still remain to be elucidated. Meanwhile, a team from McMaster University has made a complementary discovery, opening a promising avenue for treating age-related neurodegenerative diseases. This work focuses on a class of protective proteins called MANF.
In their study, supervised by Professor Bhagwati Gupta, the researchers established a link between MANFs and the maintenance of protein balance. This homeostasis, also called proteostasis, is essential for cellular functioning. It relies on various processes such as the synthesis, folding, degradation of defective proteins, as well as chemical modifications that stabilize proteins.
With age, this balance gradually becomes disrupted: cells produce proteins incorrectly and the degradation system becomes ineffective. The accumulation of abnormal proteins then ends up causing neurodegenerative pathologies. “ If cells experience stress from this protein aggregation, the endoplasmic reticulum, where proteins are made and released, receives a signal to stop their production », Explains Professor Gupta in a press release. If this stress persists, the cell risks dying, leading to neuron degeneration.
The role of MANFs in the process of eliminating defective proteins
MANFs are not unknown to researchers at McMaster University. In previous studies, their role in protection against cellular stress had already been highlighted. To deepen this knowledge, scientists studied
Caenorhabditis eleganstiny worms, and designed a system to manipulate MANF metabolism in these organisms. “ MANFs were present in structures called lysosomes, associated with protein lifespan and aggregation said team member Shane Taylor.
During this recent study, researchers identified MANFs as key players in the process of eliminating accumulated proteins. An increase in MANF levels activates a cellular cleaning system that optimizes cell function.
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« Although our work focuses on worms, it reveals universal processes », emphasizes Taylor. “ Highlighting the role of MANFs in cellular homeostasis could guide the development of new treatments for neurodegenerative diseases », concludes Gupta. This work thus opens the way to the development of promising therapeutic strategies against age-related neurodegenerative diseases.
Source : Proceedings of the National Academy of
Sciences
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