Amyloid-beta metal interaction and metal chelation.
Alzheimer's disease (AD) is associated with the abnormal aggregation of amyloid-beta (Abeta) protein. Abeta and its precursor protein (APP) interact with metal ions such as zinc, copper and iron. Evidence shows that these metals play a role in the precipitation and cytotoxicity of Abeta. Despite recent advances in AD research, there is a lack of therapeutic agents to hinder the apparent aggregation and toxicity of Abeta. Recent studies show that drugs with metal chelating properties could produce a significant reversal of amyloid-beta plaque deposition in vitro and in vivo. Here we discuss the interaction of Abeta with metals, metal dyshomeostasis in the CNS of patients with AD, and the potential therapeutic effects of metal chelators.
Cuajungco
Math P
MP
Harvard Medical School, Boston, MA 02114, USA.
Frederickson
Christopher J
CJ
Bush
Ashley I
AI
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D006801:Humans; D008667:Metalloproteins / Q000378:metabolism; D008670:Metals / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D010084:Oxidation-Reduction; D011485:Protein Binding
D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D008667:Metalloproteins; D008670:Metals