Working Paper Review Version 1 This version is not peer-reviewed

Brain-barrier Regulation, Metal (Cu, Fe) Dyshomeostasis and Neurodegenerative Disorders in Man and Animals

Version 1 : Received: 25 May 2019 / Approved: 27 May 2019 / Online: 27 May 2019 (12:27:10 CEST)

A peer-reviewed article of this Preprint also exists.

Haywood, S. Brain–Barrier Regulation, Metal (Cu, Fe) Dyshomeostasis, and Neurodegenerative Disorders in Man and Animals. Inorganics 2019, 7, 108. Haywood, S. Brain–Barrier Regulation, Metal (Cu, Fe) Dyshomeostasis, and Neurodegenerative Disorders in Man and Animals. Inorganics 2019, 7, 108.

Journal reference: Inorganics 2019, 7, 108
DOI: 10.3390/inorganics7090108

Abstract

The neurodegenerative diseases (Alzheimers, Parkinsons, amyotrophic lateral sclerosis, Huntingdons) and the prion disorders, have in common a dysregulation of metalloprotein chemistry involving redox metals (Cu,Fe,Mn). The consequent oxidative stress gives rise to protein plaques and neuronal cell death. An equilibrium exists between the functional requirement of the brain for Cu and Fe and their destructive potential with the production of reactive oxygen species.  The importance of the brain barrier is highlighted in regulating the import of these metals. Upregulation of key transporters occurs in foetal and neonatal life when brain metal requirement is high and is down-regulated in adult life when need is minimal. By contrast a neonatal mode of CTR1 upregulation persists in feral N.Ronaldsay sheep. This has led to the premise that metal regulation may return to the default setting in ageing with implications for neurodegenerative disease.

Subject Areas

blood-brain barrier; copper/iron homeostasis; neurodegenerative (Alzheimers, Parkinsons, Prion) disease; North Ronaldsay sheep

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