Cavener and his colleagues were hunting deep in the brain’s molecular machinery to discover what was going wrong there that causes the brains of patients with Alzheimer’s Disease to lose the ability to make sufficient proteins. The continual production of fresh proteins is an essential process in the brain that is necessary for learning and the long-term storage of memories.
A clue from a recent discovery showed that something was suspiciously wrong with a particular protein. This protein, called PERK, is essential for regulating protein synthesis to be at just the right level for normal brain functions. Using the brains of humans with Alzheimer’s Disease and also special “AD” mice used in research labs to model the disease in mammals, researchers had found that PERK was overactive and consequently was misregulating the synthesis of proteins.
“To determine if PERK overactivity was related to the symptoms of Alzheimer’s disease, we developed in our lab at Penn State a genetic mutation of PERK in the brains of a strain of laboratory mice,” Cavener said. Eric Klann’s laboratory at New York University, in collaboration with Cavener’s lab at Penn State, then studied how the loss of PERK in the brain influenced Alzheimer’s Disease symptoms. “Our research team found that removal of PERK from an AD mouse actually reduced AD symptoms,” Cavener said. “The learning and memory functions, which are severely impaired in AD mice, now were substantially improved when PERK was removed from the brain.” In addition, the scientists found that, within the brain, removal of PERK in AD mice also led to predicted improvement in the regulation of protein synthesis.
“Our studies suggest that reducing PERK activity in the brain of Alzheimer’s Disease patients may offer a new therapy for Alzheimer’s Disease” Cavener said. “However, such therapy would have to be specifically targeted at the brain because loss of PERK in other parts of the body, including the pancreas, can quickly lead to diabetes.”
In addition to Cavener, the study’s authors also include the study’s senior author, Eric Klann at New York University’s Center for Neural Science along with NYU researchers Tao Ma, Mimi A. Trinh, and Alyse J. Wexler; and Clarisse Bourbon, Evelina Gatti, and Philippe Pierre at the Université de la Méditerranée in Marseille, France.
The research was supported by grants from the National Institutes of Health (NS034007 and NS047834) and from the Alzheimer’s Association.
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