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2013 Grants - Xu
Roles of MiR-155/C/EBPβ/SNX27 Pathway in Alzheimer's Disease/Down Syndrome
Huaxi Xu, Ph.D.
Sanford-Burnham Medical Research Institute
La Jolla, California
2013 Down Syndrome/Alzheimer's Disease Investigator-Initiated Program
People who have Down syndrome, when in their 30s and 40s, begin to have changes in their brain that resemble those seen in people who have Alzheimer's disease. Many of those changes are believed to be associated with genes on chromosome 21, an extra copy of which occurs in people with Down syndrome. One such gene contains the blueprint for a molecule known as microRNA-155 (miR-155).
Huaxi Xu, Ph.D. and colleagues found that miR-155 suppresses a protein known as C/EBPbeta, leading to abnormally low levels of another protein known as sorting nexin 27 (SNX27). The researchers also found that SNX27 levels are low in the brains of people with Down syndrome. Mice with similarly low levels of SNX27 have impaired learning and memory, and Dr. Xu and colleagues showed that restoring SNX27 levels also restored learning and memory in these animals.
Dr. Xu and colleagues have proposed a series of studies to determine how miR-155, C/EPBbeta and SNX27 are involved in Alzheimer's disease, including the Alzheimer's-like changes that occur in people who have Down syndrome. The researchers will use molecular techniques to control the levels of those molecules in mice that have been genetically altered to have Alzheimer's-like disease. These studies will help reveal how molecules and proteins associated with Down syndrome also promote Alzheimer's-like changes in the brain, and they may help to identify new targets for drugs to prevent or slow disease progression.