New molecular tools developed in the lab of assistant professor Mi Hee Lim show promise for "cleansing" the brain of amyloid plaques, implicated in Alzheimer's disease. The research was published online Dec. 3 in the Proceedings of the National Academy of Science.

A hallmark of Alzheimer's disease - a neurodegenerative disease with no cure - is the aggregation of protein-like bits known as amyloid-beta peptides into clumps in the brain called plaques. These plaques and their intermediate messes can cause cell death, leading to the disease's devastating symptoms of memory loss and other mental difficulties.

Engineered molecules are able to disassemble misfolded amyloid clumps associated with Alzheimer's disease into smaller amyloid pieces, that can be 'cleansed' from the brain more easily

The mechanisms responsible for the formation of these misfolded proteins and their associations with Alzheimer's disease are not entirely understood, but it's thought that copper and zinc ions are somehow involved.

In earlier work, Lim and her team developed dual-purpose molecular tools that both grab metal ions and interact with amyloid-beta. The researchers went on to show that in solutions with or without living cells, the molecules were able to regulate copper-induced amyloid-beta aggregation, not only disrupting the formation of clumps, but also breaking up clumps that already had formed. 

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Morrison lab identifies protein essential for cell division in blood-forming stem cells.
Findings could lead to better cell therapies
in the future 

Sean Morrison and researchers at the U-M have discovered that a protein known to regulate cellular metabolism is also necessary for normal cell division in blood-forming stem cells. Loss of the protein results in an abnormal number of chromosomes and a high rate of cell death.

The finding demonstrates that stem cells are metabolically different from other blood-forming cells, which can divide without the protein, Lkb1. This metabolic difference could someday be used to better control the behavior of blood-forming stem cells used in disease treatments, said Sean Morrison, director of the U-M Center for Stem Cell Biology, which is based at the Life Sciences Institute.

Microscope image that shows a colony of blood-forming stem cells after seven days in culture.

"This raises the possibility that, in the future, we may be able to modulate stem cell function - when treating degenerative diseases or when performing cell therapies - by altering the metabolism of the cells," said Morrison, a Howard Hughes Medical Institute investigator. "It opens up a whole new area of inquiry that, until now, had not been recognized."

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Structure of a protein related to heart and nervous system health revealed.

May lead to smarter drug design, better understanding of a genetic disorder of the cardiovascular system

LSI research professor Janet Smith and collaborators at the U-M have solved the structure of a protein that is integral to processes responsible for maintaining a healthy heart and nervous system.

The protein structure in question is cystathionine beta-synthase, known as CBS. CBS uses vitamin B₆ to make hydrogen sulfide (H₂S), a gaseous signaling molecule that helps maintain a healthy heart and nervous system. H₂S also induces a state of suspended animation or hibernation in animals by decreasing body temperature and lowering metabolic rate.

The work to decode the structure was led by Ruma Banerjee, Ph.D., a professor in the Department of Biological Chemistry at the U-M Medical Schoool, Janet Smith, Ph.D., a research professor at the U-M Life Sciences Institute, and their colleagues. Their findings are published today in the Proceedings of the National Academy of Science.

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