Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.0
2.9
Journals
Inorganics
Special Issues
Metals in Neurodegenerative Diseases
share announcement

Metals in Neurodegenerative Diseases

A special issue of Inorganics (ISSN 2304-6740). This special issue belongs to the section "Bioinorganic Chemistry".

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 14333

Special Issue Editor

Prof. Dr. Blaine Roberts

E-Mail Website
Guest Editor
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
Interests: metalloproteomics; mass spectrometry; neurodegeneration; Alzheimer’s disease; amyotrophic lateral sclerosis; amyloid beta; biomarkers; native protein purification

Special Issue Information

Dear Colleagues,

The human brain is perhaps the most complex organ in existence. In addition to this, it has considerable and varied metabolic requirements that must be consistently maintained throughout the lifespan of an individual. This is underlined by the fact that it consumes approximately 25% of an individual’s daily energy resources, despite accounting for only 2% of total body weight. As a direct consequence of high nutrient input, the brain is rich in essential elements (particularly Fe, Cu, and Zn), with concentrations in some regions of the brain equalling or exceeding those found in the liver. Alarmingly, during neurodegeneration, the balance of essential trace elements and the metalloenzymes that use them is disrupted. Although the measurement of total essential element abundances is important, it only yields a fraction of the story. Currently, our understanding of the relationships between changes in trace elements and the function of their related metalloproteins is limited. In this Special Issue, we highlight the most current discoveries in this area: (1) The consequences of metal mis-incorporation and absence to proper protein structure and function, (2) The recent advances made in speciation techniques and their application to direct measurement of metalloenzymes, and (3) New therapeutic strategies aimed at targeting metal dyshomeostasis.

Prof. Dr. Blaine Roberts
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Inorganics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metalloproteins/metalloenzymes
  • ROS/RNS
  • neurodegeneration
  • essential minerals
  • trace elements
  • metal protein attenuating compounds
  • copper
  • iron
  • zinc
  • Alzheimer’s Disease
  • Parkinson’s Disease
  • amyotrophic lateral sclerosis
  • Wilson’s disease
  • Menkes disease

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

10 pages, 951 KiB  
Article
Copper Isotope Compositions of Superoxide Dismutase and Metallothionein from Post-Mortem Human Frontal Cortex
by Fiona Larner, Catriona A. McLean, Alex N. Halliday and Blaine R. Roberts
Inorganics 2019, 7(7), 86; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7070086 - 07 Jul 2019
Cited by 11 | Viewed by 4247
Abstract
The natural copper isotopic compositions of superoxide dismutase and metallothionein from six post-mortem human frontal cortices were determined using a combination of size exclusion protein liquid chromatography, followed by anion exchange chromatography and multiple collector inductively-coupled plasma mass spectrometry. Superoxide dismutase was enriched [...] Read more.
The natural copper isotopic compositions of superoxide dismutase and metallothionein from six post-mortem human frontal cortices were determined using a combination of size exclusion protein liquid chromatography, followed by anion exchange chromatography and multiple collector inductively-coupled plasma mass spectrometry. Superoxide dismutase was enriched in the heavier 65Cu relative to the metallothionein fraction in all specimen pairs. The isotopic compositions were independent of copper content. This finding provides evidence that nitrogen ligands in protein copper binding sites will be enriched in heavy metal isotopes, and sulphur ligands will preferentially incorporate lighter isotopes in vivo. This in turn has implications for understanding isotopic distributions within different components in the body and the dominant ligands in different tissues. Differences in Cu isotope distributions between the two proteins were seen between Alzheimer’s disease and healthy control samples, when normalised for sex. Full article
(This article belongs to the Special Issue Metals in Neurodegenerative Diseases)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

12 pages, 2407 KiB  
Review
Brain–Barrier Regulation, Metal (Cu, Fe) Dyshomeostasis, and Neurodegenerative Disorders in Man and Animals
by Susan Haywood
Inorganics 2019, 7(9), 108; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7090108 - 28 Aug 2019
Cited by 11 | Viewed by 2986
Abstract
The neurodegenerative diseases (Alzheimers, Parkinsons, amyotrophic lateral sclerosis, Huntingtons) and the prion disorders, have in common a dysregulation of metalloprotein chemistry involving redox metals (Cu, Fe, Mn). The consequent oxidative stress is associated with protein plaques and neuronal cell death. An equilibrium exists [...] Read more.
The neurodegenerative diseases (Alzheimers, Parkinsons, amyotrophic lateral sclerosis, Huntingtons) and the prion disorders, have in common a dysregulation of metalloprotein chemistry involving redox metals (Cu, Fe, Mn). The consequent oxidative stress is associated with 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 fetal and neonatal life when brain metal requirement is high, and is downregulated in adult life when need is minimal. North Ronaldsay sheep are introduced as an animal model in which a neonatal mode of CTR1 upregulation persists into adulthood and leads to the premise that metal regulation may return to this default setting in ageing, with implications for the neurodegenerative diseases. Full article
(This article belongs to the Special Issue Metals in Neurodegenerative Diseases)
►▼ Show Figures

Figure 1

18 pages, 9904 KiB  
Review
Laser Ablation Inductively Coupled Plasma Spectrometry: Metal Imaging in Experimental and Clinical Wilson Disease
by Sabine Weiskirchen, Philipp Kim and Ralf Weiskirchen
Inorganics 2019, 7(4), 54; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7040054 - 19 Apr 2019
Cited by 6 | Viewed by 6651
Abstract
Wilson disease is an inherited disorder caused by mutations in the ATP7B gene resulting in copper metabolism disturbances. As a consequence, copper accumulates in different organs with most common presentation in liver and brain. Chelating agents that nonspecifically chelate copper, and promote its [...] Read more.
Wilson disease is an inherited disorder caused by mutations in the ATP7B gene resulting in copper metabolism disturbances. As a consequence, copper accumulates in different organs with most common presentation in liver and brain. Chelating agents that nonspecifically chelate copper, and promote its urinary excretion, or zinc salts interfering with the absorption of copper from the gastrointestinal tract, are current medications. Also gene therapy, restoring ATP7B gene function or trials with bis-choline tetrathiomolybdate (WTX101) removing excess copper from intracellular hepatic copper stores and increasing biliary copper excretion, is promising in reducing body’s copper content. Therapy efficacy is mostly evaluated by testing for evidence of liver disease and neurological symptoms, hepatic synthetic functions, indices of copper metabolisms, urinary copper excretions, or direct copper measurements. However, several studies conducted in patients or Wilson disease models have shown that not only the absolute concentration of copper, but also its spatial distribution within the diseased tissue is relevant for disease severity and outcome. Here we discuss laser ablation inductively coupled plasma spectrometry imaging as a novel method for accurate determination of trace element concentrations with high diagnostic sensitivity, spatial resolution, specificity, and quantification ability in experimental and clinical Wilson disease specimens. Full article
(This article belongs to the Special Issue Metals in Neurodegenerative Diseases)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop