Selective prion protein binding to synaptic components is modulated by oxidative and nitrosative changes induced by copper(II) and peroxynitrite in cholinergic synaptosomes, unveiling a role for calcineurin B and thioredoxin

Prion diseases are a group of rare neurodegenerative disorders that develop as a result of the conformational conversion of normal prion protein (PrP C) to the disease-associated isoform (PrP Sc). The mechanism that actually causes disease remains unclear. However, the mechanism underlying the conformational transformation of prion protein is partially understood-in particular, there is strong evidence that copper ions play a significant functional role in prion proteins and in their conformational conversion. Various models of the interaction of copper ions with prion proteins have been proposed for the Cu (II)-binding, cell-surface glycoprotein known as prion protein (PrP). Changes in the concentration of copper ions in the brain have been associated with prion diseases and there is strong evidence that copper plays a significant functional role in the conformational conversion of PrP. Nevertheless, because copper ions have been shown to have both a positive and negative effect on prion disease onset, the role played by Cu (II) ions in these diseases remains a topic of debate. Because of the unique properties of paramagnetic Cu (II) ions in the magnetic field, their interactions with PrP can be tracked even at single atom resolution using nuclear magnetic resonance (NMR) spectroscopy. Various NMR approaches have been utilized to study the kinetic, thermodynamic, and structural properties of Cu (II)-PrP interactions. Here, we highlight the different models of copper interactions with PrP with particular focus on studies that use NMR spectroscopy to investigate the role played by copper ions in prion diseases.

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“…Repeated published reports noted that copper may play a significant role in the conversion of PrP C to PrP Sc [6][7][8][9] (Fig. 2).…”

Section: Introductionmentioning

confidence: 60%

“…2 ). Moreover, several reports have shown that cellular prion protein (PrP) may play a crucial role in the redox control of the neuronal environment and in the regulation of copper metabolism in a manner that contributes to disease pathology [ 7 , 10 – 12 ]. The concentration of copper in humans varies in different organs.…”

Section: Introductionmentioning

confidence: 99%

Using NMR spectroscopy to investigate the role played by copper in prion diseases

et al. 2020

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“…Calcium ion flux, as well as cytoplasmic ROS, has the potential to influence the mitochondrial retrograde signaling response (reviewed by Butow and Avadhani). 123 In addition, PrP C has been linked to both protein complex 14-3-3 100 and calcineurin B, 83 both of which are known to directly affect the regulation of the K + leak channel K2P, TRESK, which determines resting membrane excitability 124 and is the only K2P channel upregulated by a Ca 2+ -dependant pathway. This may give PrP C an indirect role in this ion channel and therefore cellular electrical excitability.…”

Section: Prpmentioning

confidence: 99%

“…82 This may be linked to an interaction with the calcineurin complex. 83 PrP C has been shown to bind to many molecules, including:…”

Section: Signal Transductionmentioning

confidence: 99%

“…Calcium ion flux, as well as cytoplasmic ROS, has the potential to influence the mitochondrial retrograde signaling response (reviewed by Butow and Avadhani). 123 In addition, PrP C has been linked to both protein complex 14-3-3 100 and calcineurin B, 83 both of which are known to directly affect the regulation of the K + leak channel K2P, TRESK, which Figure 6. PrP c modulation of intracellular ca 2+ homeostasis through g-protein-coupled purinergic (P2Y) receptors, which are activated by aTP and coupled to calcium stimulatory g-protein and to phospholipase cβ, reducing cleavage of phosphatidylinositol-bisphosphate into inositol-3-phosphate (insP 3 ).…”

mentioning

confidence: 99%

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Prion Protein Signaling in the Nervous System—A Review and Perspective

Liebert

Bicknell

Adams³

2014

Signal Transduction Insights

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Prion protein (PrP C ) was originally known as the causative agent of transmissible spongiform encephalopathy (TSE) but with recent research, its true function in cells is becoming clearer. It is known to act as a scaffolding protein, binding multiple ligands at the cell membrane and to be involved in signal transduction, passing information from the extracellular matrix (ECM) to the cytoplasm. Its role in the coordination of transmitters at the synapse, glyapse, and gap junction and in short-and long-range neurotrophic signaling gives PrP C a major part in neural transmission and nervous system signaling. It acts to regulate cellular function in multiple targets through its role as a controller of redox status and calcium ion flux.

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Survey of the year 2003 commercial optical biosensor literature

2005

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In the year 2003 there was a 17% increase in the number of publications citing work performed using optical biosensor technology compared with the previous year. We collated the 962 total papers for 2003, identified the geographical regions where the work was performed, highlighted the instrument types on which it was carried out, and segregated the papers by biological system. In this overview, we spotlight 13 papers that should be on everyone's 'must read' list for 2003 and provide examples of how to identify and interpret high-quality biosensor data. Although we still find that the literature is replete with poorly performed experiments, over-interpreted results and a general lack of understanding of data analysis, we are optimistic that these shortcomings will be addressed as biosensor technology continues to mature.

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Selective prion protein binding to synaptic components is modulated by oxidative and nitrosative changes induced by copper(II) and peroxynitrite in cholinergic synaptosomes, unveiling a role for calcineurin B and thioredoxin

Abstract: Choline acetyltransferase (ChAT) and choline transport are decreased after nitrosative stress. ChAT activity is altered in scrapie-infected neurons, where oxidative stress develops.

Cited by 8 publications

References 87 publications

Using NMR spectroscopy to investigate the role played by copper in prion diseases

Using NMR spectroscopy to investigate the role played by copper in prion diseases

Prion Protein Signaling in the Nervous System—A Review and Perspective

Survey of the year 2003 commercial optical biosensor literature

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