Prion metal interaction: Is prion pathogenesis a cause or a consequence of metal imbalance?

Rana, Anshul; Gnaneswari, Divya; Bansal, Sorav; Kundu, Bishwajit

doi:10.1016/j.cbi.2009.07.021

Cited by 31 publications

(22 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In its normal cellular form (PrPc) the protein is thought to transport copper into the cell, protect from oxidative stress and buffer copper in the cell (Westergard et al 2007) and has been shown to bind copper in vitro (Pan et al 1992). Conversion of the protein to the scrapie form (PrPsc) is induced by interaction with copper and other metal ions such as zinc, iron and manganese (Rana et al 2009) and altered metal binding by PrPsc contributes to the pathology of the consequent diseases (Wong et al 2001).…”

Section: Copper In Human Diseasementioning

confidence: 99%

Transition metal homeostasis: from yeast to human disease

2011

View full text Add to dashboard Cite

Transition metal ions are essential nutrients to all forms of life. Iron, copper, zinc, manganese, cobalt and nickel all have unique chemical and physical properties that make them attractive molecules for use in biological systems. Many of these same properties that allow these metals to provide essential biochemical activities and structural motifs to a multitude of proteins including enzymes and other cellular constituents also lead to a potential for cytotoxicity. Organisms have been required to evolve a number of systems for the efficient uptake, intracellular transport, protein loading and storage of metal ions to ensure that the needs of the cells can be met while minimizing the associated toxic effects. Disruptions in the cellular systems for handling transition metals are observed as a number of diseases ranging from hemochromatosis and anemias to neurodegenerative disorders including Alzheimer's and Parkinson's disease. The yeast Saccharomyces cerevisiae has proved useful as a model organism for the investigation of these processes and many of the genes and biological systems that function in yeast metal homeostasis are conserved throughout eukaryotes to humans. This review focuses on the biological roles of iron, copper, zinc, manganese, nickel and cobalt, the homeostatic mechanisms that function in S. cerevisiae and the human diseases in which these metals have been implicated.

show abstract

Section: Copper In Human Diseasementioning

confidence: 99%

Transition metal homeostasis: from yeast to human disease

2011

View full text Add to dashboard Cite

show abstract

“…Zinc, as copper, increases endocytosis of the prion protein causing the metal internalization and its elimination from the synaptic cleft. It has been also speculated that PrP C acts as a sensor to monitor Zn 2+ extracellular levels that may trigger a PrP C -induced signaling (Rana et al, 2009). Moreover, PrP C may affect Zn 2+ uptake via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (Watt et al, 2013).…”

Section: Prion Protein Binds Transition Metalsmentioning

confidence: 99%

Metal Dyshomeostasis and Their Pathological Role in Prion and Prion-Like Diseases: The Basis for a Nutritional Approach

Toni¹,

Massimino

Mario

et al. 2017

Front. Neurosci.

View full text Add to dashboard Cite

Metal ions are key elements in organisms' life acting like cofactors of many enzymes but they can also be potentially dangerous for the cell participating in redox reactions that lead to the formation of reactive oxygen species (ROS). Any factor inducing or limiting a metal dyshomeostasis, ROS production and cell injury may contribute to the onset of neurodegenerative diseases or play a neuroprotective action. Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of fatal neurodegenerative disorders affecting the central nervous system (CNS) of human and other mammalian species. The causative agent of TSEs is believed to be the scrapie prion protein PrPSc, the β sheet-rich pathogenic isoform produced by the conformational conversion of the α-helix-rich physiological isoform PrPC. The peculiarity of PrPSc is its ability to self-propagate in exponential fashion in cells and its tendency to precipitate in insoluble and protease-resistance amyloid aggregates leading to neuronal cell death. The expression “prion-like diseases” refers to a group of neurodegenerative diseases that share some neuropathological features with prion diseases such as the involvement of proteins (α-synuclein, amyloid β, and tau) able to precipitate producing amyloid deposits following conformational change. High social impact diseases such as Alzheimer's and Parkinson's belong to prion-like diseases. Accumulating evidence suggests that the exposure to environmental metals is a risk factor for the development of prion and prion-like diseases and that metal ions can directly bind to prion and prion-like proteins affecting the amount of amyloid aggregates. The diet, source of metal ions but also of natural antioxidant and chelating agents such as polyphenols, is an aspect to take into account in addressing the issue of neurodegeneration. Epidemiological data suggest that the Mediterranean diet, based on the abundant consumption of fresh vegetables and on low intake of meat, could play a preventive or delaying role in prion and prion-like neurodegenerative diseases. In this review, metal role in the onset of prion and prion-like diseases is dealt with from a nutritional, cellular, and molecular point of view.

show abstract

“…Recent studies have shown that PrP C increases the binding of copper to the outer plasma cell membrane and raises antioxidant enzyme activities [38], and the Cu(II)-PrPc complex appears to be redox-active with a reversible mechanism [39]. It has been observed that metal imbalance is a feature of prion disease, and metal binding to the prion protein is altered in human prion disease, a characteristic of which may be the loss of PrP C function in copper transport and homeostasis [40]. Moreover, it has been shown that a scrapie infection alters copper content at a cellular level [41] and that the copper-catalyzed redox damage of PrP C is implicated in prion disease [42].…”

Section: Introductionmentioning

confidence: 99%