PDB Molecule: Amyloid-beta precursor protein

The Amyloid-beta precursor protein (APP) is a rather large transmembrane protein, comprised of a sequence of 770 amino acids. APP is found on the surface of cells throughout the body and is responsible for many different physiological functions. Researchers believe APP has a central role in various processes, though the exact details of the protein's numerous functions are still being discovered. It is comprised of multiple domains which make the molecule flexible, and thus challenging to examine as a single intact protein. APP's fragmented form, however, garners the most attention as it is seen as a pivotal role player in Alzheimer's and other neurodegenerative disorders.

A healthy intact APP acts as a receptor on the surface of cells, capable of binding to various extracellular molecules. However, the protein is also subject to cleavage by secretases, a specific class of proteases. When APP is cleaved, peptide fragments are released. Release of one of these small peptides, known as the amyloid-beta peptide, is highly problematic. When amyloid-beta peptide is released, it changes shape and aggregates into long fibrils which then accumulate and form dangerous plaques. A buildup of these dense plaques on the surface of nerve cells leads to a disruption of normal function. The accumulation of plaque can slow nervous functions, lead to memory loss, dementia, and the onset of Alzheimer's Disease.

Though much has yet to be learned about the specifics of APP and it's fragmented peptides, they are the focus of current research. Scientists hope to target this protein and it's peptide fragments as possible sources of curing or treating debilitating neurodegenerative disorders such as Alzheimer's.