Modulating metals as a therapeutic strategy for Alzheimer's disease.
In 1906, Alois Alzheimer first characterized the disease that bears his name. Despite intensive research, which has led to a better understanding of the pathology, there is no effective treatment for this disease. Of the drugs approved by the US FDA, none are disease modifying, only symptomatic. Unfortunately, there have been a number of failed clinical trials in the past 10 years where studies show either no cognitive improvement or, worse, serious side effects associated with treatment. Hence, there is a need for the field to look at alternative approaches to therapy. In this review, we will discuss how metal dyshomeostasis occurs in aging and Alzheimer's disease. Concomitantly, we will discuss how targeting this dyshomeostasis offers an effective and novel therapeutic approach. Thus far, compounds that mediate these effects have shown great potential in both preclinical animal studies as well as in early-stage clinical trials.
The Mental Health Research Institute, The University of Melbourne, Parkville Vic 3010, Australia.
Lin W
LW
Hung
Kevin J
KJ
Barnham
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D007464:Clioquinol / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008670:Metals / Q000378:metabolism*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D028561:Transition Elements / Q000378:metabolism
D016229:Amyloid beta-Peptides; D008670:Metals; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D028561:Transition Elements; C066363:copper-thiosemicarbazone complex; D003300:Copper; D007464:Clioquinol