Aging Cell: New ways to regulate the production and degradation of A-beta have been discovered

Currently, more than 50 million people worldwide are estimated to have Alzheimer's disease.
(AD) is an aggressive, irreversible neurodegenerative disease that is the most common cause of dementia in the elderly.
amyloid-β (A beta) peptides accumulate and accumulate excessively in brain tissue, leading to the formation of extracellular aging plaques, which are thought to represent the disease's initial pathological process characterized by synhap loss and neuron damage.
A beta peptide is the product of continuous processing of β-and-γ-secretion enzymes in type I transmeral amyloid prebiotic proteins (APPs), and APP is a member of a conservative protein family that includes APP-like proteins 1 and 2 (APLP1 and APLP2).
addition to the amyloid APP processing pathway, APP can be lysed in the non-amyloid lysate cascades on which major α-and-γ-secretases depend, eliminating the production of a beta peptide.
under physiological conditions, the tight balance between the production and degradation of A-beta is necessary to prevent the accumulation of pathological A-beta.
Recently, researchers at Aging Cell studied how insulin degradation enzymes (IDEs), one of the main A-beta degradation enzymes, regulate molecular mechanisms, and how amyloid prelosor protein (APP) processing and A-beta degradation are linked in a regulatory cycle to achieve this balance.
in the absence of A-beta production caused by app or Presenilin deficiency, IDE-mediated A-beta degradation is reduced, accompanied by a decrease in IDE activity, protein levels, and expression.
similar results were obtained in cells that expressed only short-cut APP and lacked app in-cell domain (AICD), indicating that AICD promotes the expression of the IDE.
, APP overexposed mediated IDE expression increased, with similar results to overexposed C50, which represents the cells of AICD's short-cut APP.
addition to these genetic methods, the researchers also regulated IDE expression and promoter activity through AICD peptide incubation and drug suppression of γ-secretase.
results were also confirmed by the use of CRISPR/Cas9 to knock out SH-SY5Y cells from APP and Presenilin.
in the body, mice without APP or AICD had lower IDE expression in their brains, which was consistent with a significant correlation between APP expression levels and IDE expression in the human AD brain.
Therefore, the results show that there is a strong link between the production of A-beta and the degradation of A-beta, and that AICD promotes the degradation of A-beta through IDE, which itself limits its own production by degrading AICD, forming a regulatory cycle.