Redox active metals in neurodegenerative diseases

被引：72

作者：

Acevedo, Karla ^{[1
]}

Masaldan, Shashank ^{[1
]}

Opazo, Carlos M. ^{[1
]}

Bush, Ashley I. ^{[1
]}

机构：

[1] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne Dementia Res Ctr, Parkville, Vic 3052, Australia

来源：

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY | 2019年 / 24卷 / 08期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

Copper; Iron; Neurodegeneration; AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID-PRECURSOR-PROTEIN; ENDOPLASMIC-RETICULUM STRESS; INCREASED OXIDATIVE STRESS; MILD COGNITIVE IMPAIRMENT; ZINC SUPEROXIDE-DISMUTASE; TRANSGENIC MOUSE MODEL; IRON CHAPERONES PCBP1; HYPOXIA IMAGING AGENT; TARGETING A-BETA;

D O I：

10.1007/s00775-019-01731-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Copper (Cu) and iron (Fe) are redox active metals essential for the regulation of cellular pathways that are fundamental for brain function, including neurotransmitter synthesis and release, neurotransmission, and protein turnover. Cu and Fe are tightly regulated by sophisticated homeostatic systems that tune the levels and localization of these redox active metals. The regulation of Cu and Fe necessitates their coordination to small organic molecules and metal chaperone proteins that restrict their reactions to specific protein centres, where Cu and Fe cycle between reduced (Fe2+, Cu+) and oxidised states (Fe3+, Cu2+). Perturbation of this regulation is evident in the brain affected by neurodegeneration. Here we review the evidence that links Cu and Fe dyshomeostasis to neurodegeneration as well as the promising preclinical and clinical studies reporting pharmacological intervention to remedy Cu and Fe abnormalities in the treatment of Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS).

引用

页码：1141 / 1157

页数：17