The research appears as the "Paper of the Week" in the December 3 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.
One of the characteristic features of Alzheimer's disease is the deposition of amyloid β-peptides in the brain. These amyloid β-peptides are derived from a large amyloid precursor protein through a series of cleavage events. Under normal conditions, cleavage first by α-secretase and then by γ-secretase results in a soluble ectodomain, a short peptide called p3, and an intracellular C-terminal domain, none of which are amyloidogenic. Alternatively, amyloid precursor protein can be processed by the enzymes β-secretase and γ-secretase to produce a soluble ectodomain along with the full-length amyloidogenic amyloid β-peptide and the intracellular C-terminal domain.
Although amyloid precursor protein is found in many cells, its normal biological function is not well understood. "It has been suggested that amyloid precursor protein may function as a receptor or growth factor precursor," notes Dr. Xuemin Xu of The University of Tennessee. "Recent studies also suggest that the intracellular C-terminal domain of the amyloid precursor protein may function as a transcription factor."
While the exact pathogenic role of amyloid β-peptide in Alzheimer's disease has not yet been definitely established, accumulating evidence supports the hypothesis that amyloid β-peptide production and deposition in the brain could be a causative event in Alzheimer's disease. Dr. Xu explains that the literature indicates amyloid β-peptide itself could be toxic to synapses and the accumulation of amyloid β-peptide could initiate a series of events contributing
Contact: Nicole Kresge
American Society for Biochemistry and Molecular Biology