Parkinson's Disease Iron Deposition Caused by Nitric Oxide-Induced Loss of β-Amyloid Precursor Protein

被引：117

作者：

Ayton, Scott ^{[1
]}

Lei, Peng ^{[1
]}

Hare, Dominic J. ^{[1
,5
,6
]}

Duce, James A. ^{[1
,2
]}

George, Jessica L. ^{[1
]}

Adlard, Paul A. ^{[1
]}

McLean, Catriona ^{[1
,3
]}

Rogers, Jack T. ^{[4
]}

Cherny, Robert A. ^{[1
]}

Finkelstein, David I. ^{[1
]}

Bush, Ashley I. ^{[1
]}

机构：

[1] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3010, Australia

[2] Univ Leeds, Fac Biol Sci, Sch Mol & Cellular Biol, Leeds LS2 9JT, N Yorkshire, England

[3] Alfred Hosp, Dept Anat Pathol, Prahran, Vic 3004, Australia

[4] Massachusetts Gen Hosp East, Dept Psychiat Neurosci, Neurochem Lab, Charlestown, MA 02129 USA

[5] Univ Technol Sydney, Elemental Bioimaging Facil, Broadway, NSW 2007, Australia

[6] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA

来源：

JOURNAL OF NEUROSCIENCE | 2015年 / 35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：

APP; iron; nitric oxide; ANIMAL-MODELS; NEURODEGENERATION; NEUROTOXICITY; CONTRIBUTES; NEURONS; EXPORT; MICE;

D O I：

10.1523/JNEUROSCI.3439-14.2015

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Elevation of both neuronal iron and nitric oxide (NO) in the substantia nigra are associated with Parkinson's disease (PD) pathogenesis. We reported previously that the Alzheimer-associated beta-amyloid precursor protein (APP) facilitates neuronal iron export. Here we report markedly decreased APP expression in dopaminergic neurons of human PD nigra and that APP(-/-) mice develop iron-dependent nigral cell loss. Conversely, APP-overexpressing mice are protected in the MPTP PD model. NO suppresses APP translation in mouse MPTP models, explaining how elevated NO causes iron-dependent neurodegeneration in PD.

引用

页码：3591 / 3597

页数：7

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