{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:55:54Z","timestamp":1792292154160,"version":"4.4.0"},"reference-count":78,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,4,18]],"date-time":"2011-04-18T00:00:00Z","timestamp":1303084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:p>Alzheimer's disease (AD) is the most common age related neurodegenerative disease. Currently, there are no disease modifying drugs, existing therapies only offer short\u2010term symptomatic relief. Two of the pathognomonic indicators of AD are the presence of extracellular protein aggregates consisting primarily of the A\u03b2 peptide and oxidative stress. Both of these phenomena can potentially be explained by the interactions of A\u03b2 with metal ions. In addition, metal ions play a pivotal role in synaptic function and their homeostasis is tightly regulated. A breakdown in this metal homeostasis and the generation of toxic A\u03b2 oligomers are likely to be responsible for the synaptic dysfunction associated with AD. Therefore, approaches that are designed to prevent A\u03b2 metal interactions, inhibiting the formation of toxic A\u03b2 species as well as restoring metal homeostasis may have potential as disease modifying strategies for treating AD. This review summarizes the physiological and pathological interactions that metal ions play in synaptic function with particular emphasis placed on interactions with A\u03b2. A variety of therapeutic strategies designed to address these pathological processes are also described. The most advanced of these strategies is the so\u2010called \u2018metal protein attenuating compound\u2019 approach, with the lead molecule PBT2 having successfully completed early phase clinical trials. 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