Alzheimer's disease, beta-amyloid protein and zinc

Citation
Xd. Huang et al., Alzheimer's disease, beta-amyloid protein and zinc, J NUTR, 130(5), 2000, pp. 1488S-1492S
Citations number
94
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Food Science/Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF NUTRITION
ISSN journal
0022-3166 → ACNP
Volume
130
Issue
5
Year of publication
2000
Supplement
S
Pages
1488S - 1492S
Database
ISI
SICI code
0022-3166(200005)130:5<1488S:ADBPAZ>2.0.ZU;2-D
Abstract
Alzheimer's disease (AD) is characterized by amyloid deposits within the ne ocortical parenchyma and the cerebrovasculature. The main component of thes e predominantly extracellular collections, A beta, which is normally a solu ble component of all biological fluids, is cleaved out of a ubiquitously ex pressed parent protein, the amyloid protein precursor (APP), one of the typ e 1 integral membrane glycoproteins, Considerable evidence has indicated th at there is zinc dyshomeostasis and abnormal cellular zinc mobilization in AD. We have characterized both APP and A beta as copper/zinc metalloprotein s, Zinc, copper and iron have recently been reported to be concentrated to 0.5 to 1 mmol/L in amyloid plaque. In vitro, rapid A beta aggregation is me diated by Zn(ll), promoted by the alpha-helical structure of A beta, and is reversible with chelation, In addition, A beta produces hydrogen peroxide in a Cu(ll)/Fe(lll)-dependent manner, and the hydrogen peroxide formation i s quenched by Zn(ll), Moreover, zinc preserves the nontoxic properties of A beta, Although the zinc-binding proteins apolipoprotein E epsilon 4 allele and alpha(2)-macroglobulin have been characterized as two genetic risk fac tors for AD, zinc exposure as a risk factor for AD has not been rigorously studied. Based on our findings, we envisage that zinc may serve twin roles by both initiating amyloid deposition and then being involved in mechanisms attempting to quench oxidative stress and neurotoxicity derived from the a myloid mass. Hence, it remains debatable whether zinc supplementation is be neficial or deleterious for AD until additional studies clarify the issue.