The TS4NC project showed that conventional focus on the amyloid cascade hypothesis alone in Alzheimer’s Disease drug discovery research was too simplistic, and most methods, such as using antibodies to target amyloid aggregates or enzyme inhibitors aiming to modify the amyloid precursor protein (APP) processing did not improve cognitive function in clinical trials. Therefore, it is necessary to expand the panel of drug targets. Here, an alternative strategy is considered, focusing on the integration of metal ion hypothesis and oxidative stress hypothesis, given the connection between AD and redox metal dyshomeostasis. However, the drug candidate should not only act as a traditional metal chelator by simply eliminating metals from the organism, on the contrary, it performs as Metal–Protein Attenuating Compounds (MPACs) by redistributing and assisting in the restoration of brain biometal homeostasis. During this project, we were able to study such molecules and select one that we believe could serve as a basis for a promising drug candidate, not least due to the sequestration of Cu ions from their Aβ complexes and the arrest of their redox cycles, thus reducing oxidative stress in the neuronal cells, but also provides anti-inflammatory effects, delivers overall neuroprotection and put Cu back into normal physiological circulation. This synergistic project aimed to address a significant public health issue, Alzheimer’s Disease, and as such is of great interest to both public and private sectors. The results gathered from this study still require further investigation, but for now being able to select a promising tripeptide for further study is a positive outcome.
