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Archive - Mar 4, 2011

Possible Liver Origin of Alzheimer’s Plaques

Unexpected results from a Scripps Research Institute and ModGene, LLC study could completely alter scientists' ideas about Alzheimer's disease—pointing to the liver instead of the brain as the source of the "amyloid" that deposits as brain plaques associated with this devastating condition. The findings could offer a relatively simple approach for Alzheimer's prevention and treatment. The study was published online on March 3, 2011, in The Journal of Neuroscience Research. In the study, the scientists used a mouse model for Alzheimer's disease to identify genes that influence the amount of amyloid that accumulates in the brain. They found three genes that protected mice from brain amyloid accumulation and deposition. For each gene, lower expression in the liver protected the mouse brain. One of the genes encodes presenilin—a cell membrane protein believed to contribute to the development of human Alzheimer's. "This unexpected finding holds promise for the development of new therapies to fight Alzheimer's," said Scripps Research Professor Greg Sutcliffe, who led the study. "This could greatly simplify the challenge of developing therapies and prevention." In trying to help solve the Alzheimer's puzzle, in the past few years Dr. Sutcliffe and his collaborators have focused their research on naturally occurring, inherited differences in neurological disease susceptibility among different mouse strains, creating extensive databases cataloging gene activity in different tissues, as measured by mRNA accumulation. These data offer up maps of trait expression that can be superimposed on maps of disease modifier genes. As is the case with nearly all scientific discovery, Dr. Sutcliffe's research builds on previous findings.

“David and Goliath” Viruses May Shed Light on Origin of Jumping Genes

University of British Columbia researchers have identified a small virus that attacks another virus more than 100 times its own size, rescuing the infected zooplankton from certain death. The discovery may provide clues to the evolutionary origin of some jumping genes found in other organisms. The study, by UBC marine microbiologist Dr. Curtis Suttle and Ph.D. student Matthias Fischer, was published online March 3, 2011, in Science Express. It describes the marine virus Mavirus and its interaction with marine zooplankton Cafeteria roenbergenesis and CroV, the world’s largest marine virus. “It’s a microbial version of the David and Goliah story where, after infecting Cafeteria roenbergeneis, Mavirus protects it against infection by CroV, while ensuring its own survival,” said Dr. Suttle. Viruses rely on host cells to replicate; in the case of Mavirus, its host is another virus, making it only the second known virophage. It needs CroV to replicate, and in the process suppresses the propagation of CroV. “What makes this interaction significant to evolutionary biology is that the closest genetic relatives to Mavirus are mobile genetic elements found in single-celled and higher organisms,” said Dr. Suttle. “This implies that over evolutionary time, organisms have co-opted the DNA from ancient relatives of Mavirus into their own genomes, presumably so that they could acquire immunity against giant viruses like CroV. Transposons, or jumping genes, are bits of DNA that can move or “transpose” themselves to new positions within an organism’s genome. Researchers have suspected that a subset of transposons – called Maverick transposons – have a viral origin because of the nature of their DNA sequences. Suttle and Fischer’s latest work on Mavirus provides the first concrete evidence of this connection.

Varying Enzyme Activity Enhances/Erases Long-Term Memories in Rats

Even long after it is formed, a memory in rats can be enhanced or erased by increasing or decreasing the activity of a particular brain enzyme, say researchers reporting in the March 4 issue of Science. "Our study is the first to demonstrate that, in the context of a functioning brain in a behaving animal, a single molecule, PKMzeta, is both necessary and sufficient for maintaining long-term memory," explained Dr. Todd Sacktor, of the SUNY Downstate Medical Center, New York City, an author of the study, which was partially funded by the NIH. Unlike other recently discovered approaches to memory enhancement, the PKMzeta mechanism appears to work any time. It is not dependent on exploiting time-limited windows when a memory becomes temporarily fragile and changeable – just after learning and upon retrieval – which may expire as a memory grows older, said Dr. Sacktor. "This pivotal mechanism could become a target for treatments to help manage debilitating emotional memories in anxiety disorders and for enhancing faltering memories in disorders of aging," said National Institute of Mental Health (NIMH) Director Dr. Thomas R. Insel, who was not involved in the study. In earlier studies, Dr. Sacktor's team had shown that even weeks after rats learned to associate a nauseating sensation with saccharin and shunned the sweet taste, their sweet tooth returned within a couple of hours after rats received a chemical that blocked the enzyme PKMzeta in the brain's outer mantle, or neocortex, where long-term memories are stored. In the new study, the researchers paired genetic engineering with the same aversive learning model to both confirm the earlier studies and to demonstrate, by increasing PKMzeta, the opposite effect.