Is early-life iron exposure critical in neurodegeneration?

Hare, Dominic J.; Arora, Manish; Jenkins, Nicole L.; Finkelstein, David I.; Doble, Philip; Bush, Ashley I.

doi:10.1038/nrneurol.2015.100

Cited by 89 publications

(72 citation statements)

References 138 publications

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“…This finding may place iron excess as a central component in neurodegenerative processes since many neurodegenerative disorders are accompanied by iron accumulation in brain regions. Moreover, indiscriminate iron supplementation to toddlers and infants, modeled here by iron overload in the neonatal period, has been considered a potential environmental risk factor for the development of neurodegenerative disorders later in life 52 . Our findings also strongly suggest that CBD has neuroprotective effects, at least in part by blocking iron-induced apoptosis even at later stages, following iron overload, which puts CBD as a potential therapeutic agent in the treatment of neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload

et al. 2018

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Iron accumulation in the brain has been recognized as a common feature of both normal aging and neurodegenerative diseases. Cognitive dysfunction has been associated to iron excess in brain regions in humans. We have previously described that iron overload leads to severe memory deficits, including spatial, recognition, and emotional memory impairments in adult rats. In the present study we investigated the effects of neonatal iron overload on proteins involved in apoptotic pathways, such as Caspase 8, Caspase 9, Caspase 3, Cytochrome c, APAF1, and PARP in the hippocampus of adult rats, in an attempt to establish a causative role of iron excess on cell death in the nervous system, leading to memory dysfunction. Cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa, was examined as a potential drug to reverse iron-induced effects on the parameters analyzed. Male rats received vehicle or iron carbonyl (30 mg/kg) from the 12th to the 14th postnatal days and were treated with vehicle or CBD (10 mg/kg) for 14 days in adulthood. Iron increased Caspase 9, Cytochrome c, APAF1, Caspase 3 and cleaved PARP, without affecting cleaved Caspase 8 levels. CBD reversed iron-induced effects, recovering apoptotic proteins Caspase 9, APAF1, Caspase 3 and cleaved PARP to the levels found in controls. These results suggest that iron can trigger cell death pathways by inducing intrinsic apoptotic proteins. The reversal of iron-induced effects by CBD indicates that it has neuroprotective potential through its anti-apoptotic action.

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Section: Discussionmentioning

confidence: 99%

Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload

et al. 2018

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“…It has been suggested that public recommendations for AD risk reduction should caution the use of iron supplementation for those whom it is not required [18,41,42]. Dietary patterns such as a Mediterranean diet and reduced red meat consumption that associate with lower AD risk do tend to have a low iron intake, but also have other unrelated health benefits for example high intake of vegetables and low saturated fat.…”

Section: Discussionmentioning

confidence: 99%

No Genetic Overlap Between Circulating Iron Levels and Alzheimer’s Disease

Lupton

Benyamin

Proitsi

et al. 2017

JAD

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Abstract. Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect on AD risk? We evaluate the effects of peripheral iron on AD risk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control 1 Data used in the preparation of this article were obtained from the Genetic and Environmental Risk for Alzheimer's disease (GERAD1) Consortium. As such, the investigators within the GERAD1 consortia contributed to the design and implementation of GERAD1 and/or provided data but did not participate in analysis or writing of this report (except those who are named authors). Membership of the GERAD1 Consortium is provided in the Acknowledgments section.2 Data used in preparing this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators may be found at: http://adni.loni.usc.edu/wpcontent/uploads/how to apply/ADNI Acknowledgement List.pdf * Correspondence to: Michelle K. Lupton, PhD, QIMR

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“…Iron has been implicated in disorders such as Parkinson's disorder and it may be the iron levels during development that are implicated. Iron levels in tooth enamel and dentine can be directly mapped to the source and timing of infant nutrition during development of the tooth, thus providing an opportunity to correlate this with neurodegenerative disorders [ 21 ]. This retrospective method is attractive for exploring past chemical exposure during the development years.…”

Section: The Oral Environment: a Model For Other Body Systemsmentioning

confidence: 99%

Putting the Mouth into Health: The Importance of Oral Health for General Health

Peck

2016

Interface Oral Health Science 2016

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Good oral health is important to overall health and wellbeing. From the most fundamental perspectives of the oral-systemic health relationship, good oral health ensures an individual can eat, speak and socialise without pain or embarrassment. These capabilities improve an individual's wellbeing and ability to contribute to society. There are more complex oral-systemic health relationships in which poor oral health can contribute to systemic diseases including the links between orofacial disease and, for example, diabetes, cardiovascular disease, pneumonia or rheumatoid arthritis. Furthermore, the oral environment is a complex biological ecosystem which provides an opportunity to understand mechanisms underlying pathological processes and which can be a model for other body systems. Examples of these oral-systemic interactions are presented to demonstrate the importance of the orofacial environment and the need for it to be incorporated into health more broadly. By putting the mouth into health through integrated education, research and clinical care across the health disciplines, there will be advances in health that will improve individual and community health.Keywords Health • Oral-systemic health • Pain • Disability IntroduvctionThe orofacial region is unique because of its importance in social interactions, including communication and emotional expression, and in survival with mastication and lifesaving refl exes that protect other external sensory (e.g. retina, olfactory epithelium, taste receptors) and internal homeostatic (e.g. respiratory and digestive tracts) systems from damaging environmental changes. Consequently this region and good oral health are important components to overall health and wellbeing.

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Is early-life iron exposure critical in neurodegeneration?

Cited by 89 publications

References 138 publications

Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload

Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload

No Genetic Overlap Between Circulating Iron Levels and Alzheimer’s Disease

Putting the Mouth into Health: The Importance of Oral Health for General Health

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