Amyloid beta is commonly thought to be intrinsically unstructured, meaning that in solution it does not acquire a unique tertiary fold but rather populates a set of structures.
As such, it cannot be crystallized and most structural knowledge on amyloid beta comes from NMR and molecular dynamics.
β- and γ-secretase are responsible for the generation of Aβ from the release of the intracellular domain of APP, meaning that compounds that can partially inhibit the activity of either β- and γ-secretase are highly sought after.
However, familial Alzheimer disease is likely to result from altered proteolytic processing.
The gene for the amyloid precursor protein is located on chromosome 21, and accordingly people with Down syndrome have a very high incidence of Alzheimer's disease.
Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are crucially involved in Alzheimer's disease as the main component of the amyloid plaques found in the brains of Alzheimer patients.
The peptides derive from the amyloid precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ.
Aβ is formed after sequential cleavage of the amyloid precursor protein (APP), a transmembrane glycoprotein of undetermined function.
APP can be cleaved by the proteolytic enzymes α-, β- and γ-secretase; Aβ protein is generated by successive action of the β and γ secretases.
Due to its more hydrophobic nature, the Aβ42 is the most amyloidogenic form of the peptide.
However the central sequence KLVFFAE is known to form amyloid on its own, and probably forms the core of the fibril.
All cancers were shown to be associated positively with increased Aβ levels, particularly hepatic cancers.
This direction of association however has not yet been established.
Significant efforts have been focused on the mechanisms responsible for Aβ production, including the proteolytic enzymes gamma- and β-secretases which generate Aβ from its precursor protein, APP (amyloid precursor protein).Tags: Adult Dating, affair dating, sex dating