Iron in Neurodegenerative Disorders of Protein Misfolding: A Case of Prion Disorders and Parkinson's Disease

Singh, Neena; Haldar, Swati; Tripathi, Ajai K.; McElwee, Matthew K.; Horback, Katharine; Beserra, Amber

doi:10.1089/ars.2014.5874

Cited by 36 publications

(27 citation statements)

References 185 publications

(205 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Copper [20] and iron [21] appear to be primarily responsible for toxicity via oxidative-stress-type mechanisms, since they can be reversibly oxidised and reduced [22]. Oxidised forms of iron and copper bind to αSyn and trigger conformational changes associated with the formation of the amyloid plaque [23]. Reduced forms of iron and copper ions (i.e.…”

Section: Role Of Heavy Metal Ionsmentioning

confidence: 99%

The Chemistry of Neurodegeneration: Kinetic Data and Their Implications

Pavlin

Repič²,

Vianello

et al. 2015

Mol Neurobiol

View full text Add to dashboard Cite

We collected experimental kinetic rate constants for chemical processes responsible for the development and progress of neurodegeneration, focused on the enzymatic and non-enzymatic degradation of amine neurotransmitters and their reactive and neurotoxic metabolites. A gross scheme of neurodegeneration on the molecular level is based on two pathways. Firstly, reactive species oxidise heavy atom ions, which enhances the interaction with alpha-synuclein, thus promoting its folding to the beta form and giving rise to insoluble amyloid plaques. The latter prevents the function of vesicular transport leading to gradual neuronal death. In the second pathway, radical species, OH(·) in particular, react with the methylene groups of the apolar part of the lipid bilayer of either the cell or mitochondrial wall, resulting in membrane leakage followed by dyshomeostasis, loss of resting potential and neuron death. Unlike all other central neural system (CNS)-relevant biogenic amines, dopamine and noradrenaline are capable of a non-enzymatic auto-oxidative reaction, which produces hydrogen peroxide. This reaction is not limited to the mitochondrial membrane where scavenging enzymes, such as catalase, are located. On the other hand, dopamine and its metabolites, such as dopamine-o-quinone, dopaminechrome, 5,6-dihydroxyindole and indo-5,6-quinone, also interact directly with alpha-synuclein and reversibly inhibit plaque formation. We consider the role of the heavy metal ions, selected scavengers and scavenging enzymes, and discuss the relevance of certain foods and food supplements, including curcumin, garlic, N-acetyl cysteine, caffeine and red wine, as well as the long-term administration of non-steroid anti-inflammatory drugs and occasional tobacco smoking, that could all act toward preventing neurodegeneration. The current analysis can be employed in developing strategies for the prevention and treatment of neurodegeneration, and, hopefully, aid in the building of an overall kinetic molecular model of neurodegeneration itself.

show abstract

Section: Role Of Heavy Metal Ionsmentioning

confidence: 99%

The Chemistry of Neurodegeneration: Kinetic Data and Their Implications

Pavlin

Repič²,

Vianello

et al. 2015

Mol Neurobiol

View full text Add to dashboard Cite

show abstract

“…Despite these studies showing no changes in iron, there are others that suggest a strong role for PrP in iron metabolism [134]. An initial study suggested increases in both ferritin and iron response proteins in astrocytes in rodent scrapie models [135].…”

Section: Prion Diseasesmentioning

confidence: 99%

Iron, Aging, and Neurodegeneration

Angelova

Brown

2015

Metals

View full text Add to dashboard Cite

Abstract:Iron is a trace element of considerable interest to both chemistry and biology. In a biological context its chemistry is vital to the roles it performs. However, that same chemistry can contribute to a more deleterious role in a variety of diseases. The brain is a very sensitive organ due to the irreplaceable nature of neurons. In this regard regulation of brain iron chemistry is essential to maintaining neuronal viability. During the course of normal aging, the brain changes the way it deals with iron and this can contribute to its susceptibility to disease. Additionally, many of the known neurodegenerative diseases have been shown to be influenced by changes in brain iron. This review examines the role of iron in the brain and neurodegenerative diseases and the potential role of changes in brain iron caused by aging.

show abstract

“…While considerable research has focused on copper, the relation of PrP to other metals remains patchy. The three metals that have gained some interest in this regard are zinc, manganese and iron (Brown, 2011;Singh et al, 2014;Watt and Hooper, 2003). This current investigation was inspired in part by a recent paper suggesting that PrP mediated increased zinc flux through AMPA receptors (Watt et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Prion infection in cells is abolished by a mutated manganese transporter but shows no relation to zinc

Pass

Frudd

Barnett

et al. 2015

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

The cellular prion protein has been identified as a metalloprotein that binds copper. There have been some suggestions that prion protein also influences zinc and manganese homeostasis. In this study we used a series of cell lines to study the levels of zinc and manganese under different conditions. We overexpressed either the prion protein or known transporters for zinc and manganese to determine relations between the prion protein and both manganese and zinc homeostasis. Our observations supported neither a link between the prion protein and zinc metabolism nor any effect of altered zinc levels on prion protein expression or cellular infection with prions. In contrast we found that a gain of function mutant of a manganese transporter caused reduction of manganese levels in prion infected cells, loss of observable PrP(Sc) in cells and resistance to prion infection. These studies strengthen the link between manganese and prion disease.

show abstract

Iron in Neurodegenerative Disorders of Protein Misfolding: A Case of Prion Disorders and Parkinson's Disease

Abstract: Improved understanding of the relationship between brain iron imbalance and protein aggregation is likely to help in the development of therapeutic strategies that can restore brain iron homeostasis and mitigate neurotoxicity.

Cited by 36 publications

References 185 publications

The Chemistry of Neurodegeneration: Kinetic Data and Their Implications

The Chemistry of Neurodegeneration: Kinetic Data and Their Implications

Iron, Aging, and Neurodegeneration

Prion infection in cells is abolished by a mutated manganese transporter but shows no relation to zinc

Contact Info

Product

Resources

About