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Rescuing fruit flies from Alzheimer's disease
Date:7/15/2010

n FDA-approved drug used to treat other ailments in humans such as bipolar disorder.

A Potential Link to Calcium

Back in the Alzheimer's fly model, the team surmised that if they could rescue mutated flies with lithium or mGluR antagonists, that pathways downstream of mGluR might also be useful targets for rescuing age-related cognitive impairments. One pathway they investigated was the regulation of the inositol trisphosphate receptor (InsP3R), which releases calcium from internal stores into the cytoplasm of the cell.

They focused on this pathway because previous studies have found elevated calcium levels in the cells of Alzheimer's patients and more recently Dr. Kevin Foskett and his colleagues, also at Penn, had found that FAD mutations of presenilin make InsP3R more responsive to the signal that stimulates it to release calcium in the cytoplasm. (In normal situations, presenilin functions to cleave several transmembrane proteins, including the APP protein, which can produce the A-peptide found in the plaques of Alzheimer's patients.)

Jongens, McBride and their colleagues found that genetic reduction of the InsP3R pathway also prevented the age-related loss of learning and memory in the FAD fly model.

"The release of calcium from internal cellular stores during the cellular encoding of memory seems to be finely tuned so that either too much or too little calcium release could impair memory formation," notes McBride.

"Our next steps will involve validating results in a relevant mouse model of FAD or AD, as well as exploring the underlying basis for this new found connection between Fragile X Syndrome and Alzheimer's disease," says Jongens. "It is intriguing that the drugs being developed for the treatment of Fragile X might also be useful in the treatment of another disease affecting cognition, namely Alzheimer's disease."


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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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