![]() Goldstein and his colleagues found that when enzymes break off the C-terminus, kinesin is liberated and the transport process is disrupted. The C-terminus is the portion of APP where the motor molecule kinesin attaches. The scientists also found that amyloid-beta and another portion of APP, called the C- terminus, are made in these compartments inside living cells and inside compartments isolated from nerve cells. In nerve cells of the mutant mice, they found that APP, beta-secretase and other cellular cargo, in addition to the motor protein kinesin, stay mainly in the cell body, suggesting that when APP is missing, normal cell cargo transport is stalled. The scientists compared cell transport in neurons of normal mice and mutant mice in which the APP protein is missing. Finding them together inside the cell suggests that APP processing may be part of a normal cell transport function that is somehow disrupted in Alzheimer’s disease, according to Goldstein. Beta-secretase and presenilin-1 are thought to be the main enzymes that process APP and create amyloid-beta peptide. Goldstein and his colleagues have studied this process and conclude that APP may be involved in a signaling process that leads to cell death when nerve cells are damaged.įurthermore, the scientists discovered that two other key Alzheimer’s-disease-related proteins, beta-secretase and presenilin-1, are found together with APP inside the packet. When something goes wrong with this transport process, the cell often cannot cope and sends out a distress signal that initiates cell death. “The cell would have to ship cargo along rather narrow 20-foot pipes and keep track of everything that is happening along the route.” “If you imagine the cell body as a 50-foot room, the axon could extend up to 200 miles away,” he said. Communication in these cells is long distance, explained Goldstein. ![]() This cell transport mechanism is crucial to nerve cells, which have the unique property of sending out tendrils, called axons, up to several feet from the main cell body to innervate distant parts of the body. Using mouse neurons as a model, the scientists showed that APP serves as an attachment point for a molecular motor called kinesin, which transports packets of protein from the main cell body along the length of the cell. Goldstein and his colleagues studied the role of amyloid precursor protein (APP), which gives rise to the abnormal amyloid clumps. In the brains of patients with Alzheimer’s disease, a peptide called amyloid-beta accumulates in areas of the brain where nerve cells die en masse, leading to progressive dementia. ![]() Neurologists see protein aggregations in diseased brains, but there is a big gulf in understanding whether the generation of protein aggregates causes the disease per se.” “This has been much less useful so far in understanding neurodegenerative diseases. ![]() “If you look at the history of breakthroughs in disease, often the understanding of what proteins normally do gives important clues to what is aberrant in disease,” said Goldstein. If you look at the history of breakthroughs in disease, often the understanding of what proteins normally do gives important clues to what is aberrant in disease.
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