Anavex Life Sciences Corp (AVXL)

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Is a-beta protein misfolded protein?

Amyloid beta (Aß) is often called a protein. But it is not a protein. It is a peptide. It is a fragment of the protein called Amyloid Precursor Protein (APP)

Normally, the concept of protein misfolding applies to newly formed protein. Part of the job of the endoplasmic renticulum and certain types of proteins that are chaperone proteins work to prevent protein from misfolding. Think of the newly produced protein as being a long roll of fly paper. That fly paper has to be kept stretched out so that it does not stick together in the wrong place. When the protein is carried to a part of the endoplasmic renticulum where it is folded into the correct 3D structure. Only after it is folded, will it work correctly. Due to just how "sticky" newly formed protein is, keeping it from misfolding is difficult and most newly formed protein does misfold. Then it has to be taken back apart. When the cells become stressed and can no longer dispose of misfolded protein or too much protein is misfolded such that the cell can't produce enough correctly folded protein, then there are problems.

With Aß, the problem is that when neurons have metabolic problems.They may form excess APP which is used in the repair and maintenance of synaptic junctions. The APP may not even get used due to the metabolic problems and gets broken down to Aß. But due to the same metabolic problems, the Aß is not quickly further metabolized and removed from the cells and extracellular areas. Therefore, it accumulates, and can form "sticky" structures that accumulate in size and tend to poison neurons and other cells.

If the cell were healthy and in "homeostasis", the excess Aß would be metabolized (broken down even smaller) and removed from the cells and extracellular spaces.