Alzheimer's disease, metal ions and metal homeostatic therapy

被引:297
作者
Zatta, Paolo [1 ]
Drago, Denise [1 ]
Bolognin, Silvia [1 ]
Sensi, Stefano L. [2 ,3 ]
机构
[1] Univ Padua, Dept Biol, CNR, Inst Biomed Technol,Padua Metalloprot Unit, I-35121 Padua, Italy
[2] Univ G DAnnunzio, CeSI Ctr Excellence Aging, Mol Neurol Unit, Dept Basic & Appl Med Sci, I-66013 Chieti, Italy
[3] Univ Calif Irvine, Dept Neurol, Irvine, CA 92697 USA
关键词
BLOOD-BRAIN-BARRIER; AMYLOID-BETA-PEPTIDE; TRANSGENIC MOUSE MODEL; TARGETING A-BETA; IN-VIVO; NEURODEGENERATIVE DISORDERS; MITOCHONDRIAL DYSFUNCTION; METALLOTHIONEIN-III; HIPPOCAMPAL-NEURONS; INTRACELLULAR ZINC;
D O I
10.1016/j.tips.2009.05.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Mounting evidences support the idea that endogenous 'biometals', such as copper, iron, zinc and exogenous ones such as aluminum, can be involved as factors or cofactors in the etiopathogenesis of a variety of neurodegenerative diseases. Alzheimer's disease (AD) is a multifactorial neurodegenerative condition associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. In AD, the process of beta-amyloid (A beta) misfolding and plaque aggregation is greatly influenced by alterations in the homeostasis of the aforementioned metal ions. Here, we discuss the most recent evidences that associate metal ion dyshomeostasis with the development of AD. As for aluminum, a role for this ion in AD pathogenesis is still controversial. Thus, here, we also critically review new findings that argue for and against the 'aluminum hypothesis'. Finally, it is discussed how therapeutic strategies aimed at restoring metal homeostasis can delay and modify the progression of AD-related neurodegeneration.
引用
收藏
页码:346 / 355
页数:10
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