Researchers find "weak link" in Alzheimer's therapies

Over the years, scientists have found it extremely difficult to advance new research on Alzheimer's, as they don't really know how the disease works or how to stop it. And now, researchers from the University of California, San Diego believe that current therapies being investigated for Alzheimer's disease may cause further neural degeneration and cell death. This finding "would result in a paradigm shift" in the understanding of the molecular mechanism underlying Alzheimer's disease, says Brigita Urbanc, professor of biophysics at Drexel University, who was not involved in this study, in an email to The Scientist.

By combining 3-D computer simulations with high resolution atomic force microscopy membrane protein and cell imaging, electrical recording and various cellular assays, UCSD nano-biophysicist Ratnesh Lal and his colleagues investigated the structure and function of truncated peptides--known as nonamyloidgenic peptides--formed by some Alzheimer's drug candidates. The researchers found that the nonamyloidgenic peptides formed active ion channels that caused the cells to take in very high levels of calcium ions, which damaged synaptic efficiency and eventually killed the neurons that are linked to memory loss in human brain, according to a UCSD release.

"There are several drugs to treat Alzheimer's in Trials I and II, but we don't believe that they will be adopted for clinical usage," says Lal, a joint professor in the UCSD Jacobs School of Engineering's Department of Mechanical and Aerospace Engineering and Bioengineering. "We believe we are providing the most direct mechanism of Alzheimer's disease and Down Syndrome pathology. Through our research we have provided a structure and mechanism (an ion channel) that can account for the pathology. The strategy to control the activity of this structure--the opening and closing of the channel--should be targeted for an effective treatment." 

Lal and his colleagues are now working on a 3D structural model of the ion channel using their data to identify the domains (or sites) of the channel for designing effective therapeutics.  

- see the release
- text of the study is available here
- get more from The Scientist

ALSO: Your brain's capacity for information is a reliable predictor of Alzheimer's disease and can be cheaply and easily tested, according to scientists. "We have developed a low-cost behavioral assessment that can clue someone in to Alzheimer's disease at its earliest stage," says Michael Wenger, associate professor of psychology at Penn State. "By examining (information) processing capacity, we can detect changes in the progression of mild cognitive impairment (MCI)." Release

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