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An international team of researchers proposed that the translational regulatory protein called eIF5-mimic protein (5MP) protects the brain against neuronal decay, which may lead to neurodegenerative disorders, according to a new study.

Medical Xpress reported that the genetic material is translated at rapid rates with extreme precision to reproduce and repair damage during cell division. However, sometimes this process could also deregulate and develop diseases. Byproducts of this deregulation could break down the repair mechanisms of cells and cause further damage, such as Alzheimer's disease.

International researchers have found that the 5MP translational protein implicated in tumor growth can help regulate the deregulation of cellular translation and protect against neuronal decay.

Protein Involved in Tumor Growth May Help Protect Against Neuronal Decay, Prevent Neurodegeneration
(Photo: Wikimedia Commons)
The β-Secretase (BACE-1). The distinctive role of BACE-1 in Alzheimer’s disease pathogenesis has made it a validated target to develop anti-Alzheimer agents.

Neurodegeneration May Be Caused by Toxic Peptide Products

Lead researcher Katsura Asano, a professor in the Graduate School of Integrated Sciences for Life at Hiroshima University, said that age-related neurodegenerative diseases may be caused by the slow and steady accumulation of toxic peptide products.

Asano added that, repeat-associated non-AUG (RAN) translation is one of the mechanisms that play a significant role in generating toxic products.

According to Medical Xpress, cells look for specifically ordered markers during cell division to replicate genetic material. These markers signal the spot where replication should start and end the copy to make a specific protein.

Typically, the pattern should be AUG but RAN translation does not necessarily need this signal. They can begin processing at some points and end up copying bits of repeated genetic information that becomes toxic buildup and leads to neurodegeneration.

A paper in Cold Spring Harbor Perspectives in Biology suggests that over 40 different neurodegenerative disorders are caused by toxic repeat peptide products within translated and non-translated gene regions.

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5MP Protein Prevents Neurodegeneration

The study, titled "Human Oncoprotein 5mp Suppresses General and Repeat-Associated Non-AUG Translation via eIF3 by a Common Mechanism," published in Cell Reports, highlights the role of 5MP protein in controlling RAN translation that could produce toxic repeat peptide products.

According to Hiroshima University's news release, Asano's study shows that the novel translational regulatory protein, 5MP, protects neural decay by preventing RAN translational that results in deleterious peptides.

Asano collaborated with Peter Todd's lab at the University of Michigan and used a fly disease model to demonstrate the process. They also collaborated with other scientists from Virginia Commonwealth University and Kumamoto University.

In healthy conditions, 5MP is involved in regulating RAN translation, but researchers found in their research that it competes with the protein that mimics human cells. When 5MP wins, it reduces toxic byproducts of RAN translation and enhances the lifespan of their test subjects, according to Medical Xpress.

"Taken together, these data suggest that modulation of 5MP levels could be a viable therapeutic target by which to selectively reduce RAN translation in repeat expansion disorders," the news outlet quoted Asano. "More studies on 5MP and the mechanism of translation can greatly contribute to the understanding and care of neurodegenerative diseases," the researcher added.

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