Hematology

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PUBLIC PAGE
Thu, Jun 1, 2017 1:00pm

Cell Research on Amyloidosis

By Mayo Clinic Hematology Staff, @mayoclinichematologystaff

Lab Worker Doing Research

When proteins fold improperly, the consequences can be dire.

At Mayo Clinic, Marina Ramirez-Alvarado, Ph.D., studies one type of protein abnormality associated with a complex and incurable disease called light chain amyloidosis. This type of amyloidosis is the most common and can affect the heart, kidneys, skin, nerves, and liver. Dr. Ramirez-Alvarado

Dr. Ramirez-Alvarado and her team just published a paper on their most recent findings in the Journal of Biological Chemistry.

In the paper, Dr. Ramirez-Alvarado and her team use live cell fluorescence microscopy to show how these abnormal proteins invade cells.

Abnormal Antibodies
In light chain amyloidosis, the proteins in question are produced within the body’s bone marrow. Bone marrow contains white blood cells called plasma cells that are responsible for manufacturing antibodies. Antibodies are large Y-shaped proteins that help the immune system identify and neutralize pathogens. Antibodies are made up of two parts: “light chain” proteins in the two arms of the Y, and “heavy chain” proteins for the base of the Y.

Antibody Protein Deposits
As people age, plasma cells can change. Some of those changes can cause the cells to create only light chain proteins. These snippets of antibody proteins are released into the bloodstream where they preferentially bind to other light chains to form amyloid fibrils, fibrous protein deposits that clump together outside of cells in tissues and organs.

AL09 Fibrils

These cells with red-stained nuclei are incubated with amyloid fibrils. Over time these fibrous protein deposits gather around the cell membranes and promote cell clustering. This clustering effect increases over time and interfere with the normal growth of the cells. Together these clumps somehow penetrate cells and cause them to die.

Together these clumps somehow penetrate cells and cause them to die.

“Learning how the protein and fibrils attack the cell which creates clumps that result in the death of the organ provides tremendous insight,” explains Dr. Ramirez-Alvarado. “We can look at inhibitors that could be used to block the penetration of the protein and amyloid fibrils into the cells.”

To learn more about how this affects you, the patient, read the entire article on Discovery's Edge.

I am working through the dX snail route toward a diagnosis of Amyloidosis. I have written a report of the medical and other issues so far involved. It is built around your staff’s book on “Amyloidosis -Diagnosis and Treatment, and on the work of ALNYLAM. I you are interested, you can access my paper by contacting me via personal message.

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