Amyloid beta-peptides are sticky, neurotoxic protein fragments that accumulate, kill nerve cells, and clump together to form the distinctive amyloid plaques in the brains of people with Alzheimer's disease. They are generated when a larger, normal protein called amyloid precursor protein (APP) is cleaved or split in a series of events. A protein complex called the presenilin complex is responsible for the final cleavage event.
Presenilin complexes are thought to cause an unusual form of protein cleavage in which selected membrane proteins are split in a region that crosses cell membranes. This previously unrecognized form of protein cleavage is essential for several normal signaling processes.
The same presenilin complex also generates amyloid-beta from APP. The presenilin cleavage that generates amyloid-beta may be a physiological process unrelated to signaling. In fact, it may just be a way to remove unneeded protein stubs from cellular membranes.
However, new findings from Howard Hughes Medical Institute (HHMI) international research scholar Peter St George-Hyslop at the University of Toronto argue against this hypothesis. St George-Hyslop's group recently pinpointed a new component called TMP21 that controls presenilin's dicing tendencies, preventing it from snipping apart APP. The researchers report their findings in the April 27, 2006, issue of the journal Nature.
When TMP21 was first discovered, it appeared to be a "cargo transporter" that embeds itself in the membranes of transport vesicles--small, bladder-like sacs that shuttle proteins from one cellular locale to another. St George-Hyslop's group discovered that TMP21 moo
Contact: Jennifer Donovan
Howard Hughes Medical Institute