After decades of research the molecular bases of AD are still under intense discussion.
The key features of neuropathology, such as fibril assembly and oligomer neurotoxic activity, are shared between AD and other neurodegenerative diseases, which are caused by peptides nonhomologous to Aβ.
IDE is a culprit of the Aβ degradation with remarkable extracellular/intracellular omnipresence. IDE’s activity in the brain decreases with age and during early stages of AD.
IDE is a protease specific to β-structure-forming aggregation-prone peptides with a growing list of substrates, including those of FBD/FDD.
Noncompetitiveness and high specificity are the important advantages of prospected allosteric drugs. The recently proposed idea of allosteric mutations was shown to be instrumental in specific activation of IDE against Aβ.
After decades of research and clinical trials there is still no cure for Alzheimer’s disease (AD). While impaired clearance of amyloid beta (Aβ) peptides is considered as one of the major causes of AD, it was recently complemented by a potential role of other toxic amyloidogenic species. Insulin-degrading enzyme (IDE) is the proteolytic culprit of various β-forming peptides, both extracellular and intracellular. On the basis of demonstrated allosteric activation of IDE against Aβ, it is possible to propose a new strategy for the targeted IDE-based cleansing of different toxic aggregation-prone peptides. Consequently, specific allosteric activation of IDE coupled with state-of-the-art compound delivery and CRISP-Cas9 technique of transgene insertion can be instrumental in the fight against AD and related neurodegenerative maladies.