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2014 Grants - Cai Q
Regulation of Synaptic ABeta Generation via BACE1 Retrograde Transport in Alzheimer’s Disease
Qian Cai, M.D., Ph.D.
Rutgers, The State University of New Jersey
Piscataway, New Jersey
2014 New Investigator Research Grant
Abeta (also known as beta-amyloid) is a protein fragment thought to play an important role in the development of Alzheimer’s disease. It is produced from its parent protein by the action of other proteins that work as molecular scissors, one of which is beta-secretase 1 (BACE1). Accumulation of beta-amyloid and its clumping into amyloid plaques are key features of Alzheimer’s disease in the brain.
Synapses are specialized structures through which nerve cells send rapid signals to other cells, giving the brain many of its unique abilities. They are essential for learning and memory and are damaged in the early stages of Alzheimer’s disease. There is evidence that BACE1 accumulates to abnormally high levels in the synapses of people with Alzheimer’s disease.
Qian Cai, M.D., Ph.D., and colleagues have found evidence that this accumulation of BACE1 in the synapses may be related to defects in a cellular process called “retrograde transport.” This process moves proteins and other molecules away from the synapses and back to the center of the cell called the cell body. They have proposed to advance their studies by exploring proteins involved in the transport of BACE1 back to the cell body, and how those proteins are affected in Alzheimer’s disease. Using mice genetically altered to have an Alzheimer’s-like condition, the researchers plan to restore the function of transport proteins to determine if it helps prevent the accumulation of BACE1 and beta-amyloid in nerve cell synapses. These studies will advance our understanding of why beta-amyloid accumulates at synapses, and they may suggest ways to develop treatments that inhibit that accumulation and perhaps slow or prevent Alzheimer’s disease progression.