Metals and Alzheimer's disease.
There is increasing evidence to support a role for both the amyloid beta-protein precursor (AbetaPP) and its proteolytic fragment, amyloid beta (Abeta), in metal ion homeostasis. Furthermore, metal ions such as zinc and copper can interact with both AbetaPP and Abeta to potentiate Alzheimer's disease by participating in the aggregation of these normal cellular proteins and in the generation of reactive oxygen species. In addition, metal ions may interact on several other AD-related pathways, including those involved in neurofibrillary tangle formation, secretase cleavage of AbetaPP and proteolytic degradation of Abeta. As such, a dysregulation of metal ion homeostasis, as occurs with both aging and in AD, may foster an environment that can both precipitate and accelerate degenerative conditions such as AD. This offers a broad biochemical front for novel therapeutic interventions.
Adlard
Paul A
PA
The Oxidation Disorders Laboratory, The Mental Health Research Institute, Parkville, Victoria, 3052, Australia. padlard@mhri.edu.au
Bush
Ashley I
AI
D000368:Aged; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003035:Cobalt / Q000097:blood* / Q000378:metabolism; D003300:Copper / Q000097:blood* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007501:Iron / Q000097:blood* / Q000378:metabolism; D013058:Mass Spectrometry; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015032:Zinc / Q000097:blood* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C444321:amyloid beta-protein (1-34); D003035:Cobalt; D003300:Copper; D007501:Iron; D015032:Zinc