Hare Dominic J, Cardoso Bárbara Rita, Raven Erika P, Double Kay L, Finkelstein David I, Szymlek-Gay Ewa A, Biggs Beverley-Ann
Department of Medicine (Royal Melbourne Hospital) at the Doherty Institute, The University of Melbourne, Parkville, Melbourne, VIC Australia.
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Melbourne, VIC Australia.
NPJ Parkinsons Dis. 2017 Jan 5;3:1. doi: 10.1038/s41531-016-0004-y. eCollection 2017.
Iron accumulates gradually in the ageing brain. In Parkinson's disease, iron deposition within the substantia nigra is further increased, contributing to a heightened pro-oxidant environment in dopaminergic neurons. We hypothesise that individuals in high-income countries, where cereals and infant formulae have historically been fortified with iron, experience increased early-life iron exposure that predisposes them to age-related iron accumulation in the brain. Combined with genetic factors that limit iron regulatory capacity and/or dopamine metabolism, this may increase the risk of Parkinson's diseases. We propose to (a) validate a retrospective biomarker of iron exposure in children; (b) translate this biomarker to adults; (c) integrate it with in vivo brain iron in Parkinson's disease; and (d) longitudinally examine the relationships between early-life iron exposure and metabolism, brain iron deposition and Parkinson's disease risk. This approach will provide empirical evidence to support therapeutically addressing brain iron deposition in Parkinson's diseases and produce a potential biomarker of Parkinson's disease risk in preclinical individuals.
铁在衰老大脑中逐渐积累。在帕金森病中,黑质内的铁沉积进一步增加,导致多巴胺能神经元中的促氧化环境增强。我们推测,在高收入国家,由于谷物和婴儿配方奶粉历来都添加了铁,个体在生命早期接触铁的量增加,这使他们易患与年龄相关的大脑铁积累。再加上限制铁调节能力和/或多巴胺代谢的遗传因素,这可能会增加患帕金森病的风险。我们建议:(a)验证儿童铁暴露的回顾性生物标志物;(b)将该生物标志物应用于成年人;(c)将其与帕金森病患者体内的脑铁整合;(d)纵向研究生命早期铁暴露与代谢、脑铁沉积和帕金森病风险之间的关系。这种方法将提供实证依据,以支持在帕金森病中针对脑铁沉积进行治疗,并产生一种临床前个体帕金森病风险的潜在生物标志物。