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Scientists discover molecular link between circadian clock disturbances and inflammatory diseases
Date:8/1/2012

matory proteins known as cytokines, including interleukin-6 and tumor necrosis factor-α, compared to mice with CRY genes.

"Our findings demonstrate that a lack of cryptochrome activates these proinflammatory molecules, indicating a potential role for cryptochrome in the regulation of inflammatory cytokine expression," says Satchidananda Panda, an associate professor in Salk's Regulatory Biology Laboratory and one of the senior authors of the study.

In addition, the researchers found that a lack of CRY activated the NF-kB pathway, a molecular signaling conduit that controls many genes involved in inflammation. NF-kB is a protein complex in a cell's cytoplasm, "just happily doing nothing," says Verma. In response to stimuli, it is transferred to the cell's nucleus, where it binds to inflammation genes and turns them on. The regulation of these genes is tightly controlled, but NF-kB does not completely shut off their expression. This lingering expression causes inflammation.

"Every time this pathway is turned on, there is a residual amount of inflammation left in the body," says Rajesh Narasimamurthy, a research associate in Verma's laboratory and the paper's first author. "That adds up over time, contributing to inflammation-related diseases like obesity and diabetes."

Previous research has shown that suppressing the activity of the NF-kB pathway might be a suitable therapy for some diseases. For example, NF-kB is activated automatically in cancer cells of multiple myeloma, which affects infection-fighting plasma cells in the bone marrow and allows the cells to proliferate. Drugs that inhibit this activity might be able to degrade NF-kB to the point that it may kill off the disease.

The researchers say the goal now is to find out how to suppress NF-kB activation in the short term to treat diseases like diabetes. They caution that any long-term suppression of the pathway could lead to chronic infection. "We would like
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Contact: Andy Hoang
AHoang@salk.edu
619-861-5811
Salk Institute
Source:Eurekalert  

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