|
||||||||
|
MILESTONE SYMPOSIUM 4
Speakers Unmask Molecular Players in the BrainPrions--the culprits behind mad cow disease and its human equivalent, Creutzfeldt- Jakob disease--may turn out to be molecules of the Jekyll-Hyde variety. The tiny snippets of misshapen protein are thought to cause disease by endlessly replicating inside cells, clogging and eventually killing them. It now appears that the prion's penchant for self-propagation may work to the brain's advantage. Eric Kandel and his colleagues have recently discovered that a protein involved in long-term memory contains a prionlike domain. This domain may allow the protein, CPEB, to continuously function, though at a low level.
Eric Kandel and his colleagues have discovered that prions may play an important role in long-term memory. (Photo by Phil Farnsworth) "This provides a notion about how memories can keep going in perpetuity at a selected synapse," said Kandel, winner of the 2000 Nobel Prize in Physiology or Medicine. He was speaking on Dec. 4 at the fourth Milestone Symposium, "Molecular Sensing in the Brain." (Weeks later, Kandel and colleagues had two widely publicized papers in the Dec. 26 Cell detailing this research.) "Prions are normally thought of as disease proteins, but they may actually be physiologically active in the normal brain," he said. Prions were not the only proteins that were cast in a new light at the symposium. Several years ago, Carla Shatz and her colleagues discovered that the well-known immune system molecules, MHC class I, play a key role in the developing brain by helping neurons make the right connections. This came as a surprise since the brain was thought to be exempt from surveillance or occupation by immune system proteins. MHC class I now appears to control the size of synaptic boutons, said Shatz, the Nathan Marsh Pusey professor of neurobiology at HMS. These molecules also appear to play a role in synaptic plasticity and remodeling--activities that, Shatz reminded the audience, go on through our lifetimes. "Even now your brain is different from the way it was before this seminar started, whether you like it or not," she said. As for what causes such change, most people would be tempted to look outside the brain to external sensory stimuli. Yet, as John Assad observed, the brain is a dynamic player. This is true even at the level of the processing of retinal images. "Not only does vision inform the brain, the brain informs vision," said Assad, HMS associate professor of neurobiology. A single stimulus can produce more than one perception in the brain, and indeed, many of the images our brains receive are ambiguous. Assad, whose work focuses on figuring out how the brain handles such bistable stimuli, has recently found some clues in the lateral inferior parietal area of the brain. "In the long run, we want to understand the molecular mechanisms for the switch from retinal representations to more subjective perception," he said. Several speakers made clear that unmasking the molecular players in complex visual processing, memory, and other brain activities is more than an intellectual exercise. Kandel, whose recent prion discovery follows decades of research into the molecular basis of memory, has helped found a company, Memory Pharmaceuticals, with the goal of developing memory-supporting therapies. "I would think it very likely that in five or ten years we will have drugs that will be helpful for age-related memory loss," he said. --Misia Landau |
