Prion protein prevents heavy metals overloading of cells and thus protects them against their toxicity

Prčina, M; Kontseková, Eva; Novák, Michal

doi:10.4149/av_2015_02_179

Cited by 3 publications

(3 citation statements)

References 29 publications

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“…370 It has been shown that the protein is involved in several cellular processes including neuroprotection against excitotoxicity and serum starvation, 371 proliferation and cell-cell adhesion, 370, 372 formation of synapses 373 and ligand binding. 374, 375 PrP can protect cells against heavy metal overloading and subsequent oxidative stress by binding divalent ions of copper, zinc, manganese and nickel. 375 Due to the ability of PrP to modulate cell proliferation and apoptosis it is believed to play a role on cancer development.…”

Section: Prions and Prion Diseasesmentioning

confidence: 99%

“…374, 375 PrP can protect cells against heavy metal overloading and subsequent oxidative stress by binding divalent ions of copper, zinc, manganese and nickel. 375 Due to the ability of PrP to modulate cell proliferation and apoptosis it is believed to play a role on cancer development. 376 Indeed, increased PrP C level has been found in gastric cancer, 377 colorectal cancer 378 and skin cancer.…”

Section: Prions and Prion Diseasesmentioning

confidence: 99%

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Implications of peptide assemblies in amyloid diseases

et al. 2017

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Neurodegenerative disorders and type 2 diabetes are global epidemics compromising the quality of life of millions worldwide, with profound social and economic implications. Despite the significant differences in pathology – much of which are poorly understood – these diseases are commonly characterized by the presence of cross-β amyloid fibrils as well as the loss of neuronal or pancreatic β-cells. In this review, we document research progress on the molecular and mesoscopic self-assembly of amyloid-beta, alpha synuclein, human islet amyloid polypeptide and prions, the peptides and proteins associated with Alzheimer’s, Parkinson’s, type 2 diabetes and prions diseases. In addition, we discuss the toxicities of these amyloid proteins based on their self-assembly as well as their interactions with membranes, metal ions, small molecules and engineered nanoparticles. Through this presentation we show the remarkable similarities and differences in the structural transitions of the amyloid proteins through primary and secondary nucleation, the common evolution from disordered monomers to alpha-helices and then to β-sheets when the proteins encounter the cell membrane, and, the consensus (with a few exceptions) that off-pathway oligomers, rather than amyloid fibrils, are the toxic species regardless of the pathogenic protein sequence or physicochemical properties. In addition, we highlight the crucial role of molecular self-assembly in eliciting the biological and pathological consequences of the amyloid proteins within the context of their cellular environments and their spreading between cells and organs. Exploiting such structure-function-toxicity relationship may prove pivotal for the detection and mitigation of amyloid diseases.

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Section: Prions and Prion Diseasesmentioning

confidence: 99%

Section: Prions and Prion Diseasesmentioning

confidence: 99%

Implications of peptide assemblies in amyloid diseases

et al. 2017

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“…In addition, PrP C is involved in copper transport and in cell defense mechanisms against oxidative insult, through the regulation of the intracellular CuZn superoxide dismutase activity (Cu-Zn SOD), protecting cells against heavy metals overload and subsequent oxidative stress [24,26]. Moreover, it has been suggested that overexpressed PrP C could be interpreted as a molecular marker of cell Cu deficiency [48, 49,50]. Thus, if morphine withdrawal promotes an increase of ROS molecules, we can hypothesize that enhanced expression of hippocampal PrP C may be considered as a phenomenon reflecting the ability of PrP C to link Cu 2+ and, in turn, to activate Cu-Zn SOD.…”

Section: Discussionmentioning

confidence: 99%

Morphine Withdrawal Modifies Prion Protein Expression in Rat Hippocampus

Mattei¹,

Martellucci²,

Santilli³

et al. 2017

PLoS ONE

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The hippocampus is a vulnerable brain structure susceptible to damage during aging and chronic stress. Repeated exposure to opioids may alter the brain so that it functions normally when the drugs are present, thus, a prolonged withdrawal might lead to homeostatic changes headed for the restoration of the physiological state. Abuse of morphine may lead to Reacting Oxygen Species-induced neurodegeneration and apoptosis. It has been proposed that during morphine withdrawal, stress responses might be responsible, at least in part, for long-term changes of hippocampal plasticity. Since prion protein is involved in both, Reacting Oxygen Species mediated stress responses and synaptic plasticity, in this work we investigate the effect of opiate withdrawal in rats after morphine treatment. We hypothesize that stressful stimuli induced by opiate withdrawal, and the subsequent long-term homeostatic changes in hippocampal plasticity, might modulate the Prion protein expression. Our results indicate that abstinence from the opiate induced a time-dependent and region-specific modification in Prion protein content, indeed during morphine withdrawal a selective unbalance of hippocampal Prion Protein is observable. Moreover, Prion protein overexpression in hippocampal tissue seems to generate a dimeric structure of Prion protein and α-cleavage at the hydrophobic domain. Stress factors or toxic insults can induce cytosolic dimerization of Prion Protein through the hydrophobic domain, which in turn, it stimulates the α-cleavage and the production of neuroprotective Prion protein fragments. We speculate that this might be the mechanism by which stressful stimuli induced by opiate withdrawal and the subsequent long-term homeostatic changes in hippocampal plasticity, modulate the expression and the dynamics of Prion protein.

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Prion protein scrapie and the normal cellular prion protein

Atkinson

Zhang

Munn

et al. 2015

Prion

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ABSTRACT. Prions are infectious proteins and over the past few decades, some prions have become renowned for their causative role in several neurodegenerative diseases in animals and humans. Since their discovery, the mechanisms and mode of transmission and molecular structure of prions have begun to be established. There is, however, still much to be elucidated about prion diseases, including the development of potential therapeutic strategies for treatment. The significance of prion disease is discussed here, including the categories of human and animal prion diseases, disease transmission, disease progression and the development of symptoms and potential future strategies for treatment. Furthermore, the structure and function of the normal cellular prion protein (PrP C ) and its importance in not only in prion disease development, but also in diseases such as cancer and Alzheimer's disease will also be discussed.

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Prion protein prevents heavy metals overloading of cells and thus protects them against their toxicity

Cited by 3 publications

References 29 publications

Implications of peptide assemblies in amyloid diseases

Implications of peptide assemblies in amyloid diseases

Morphine Withdrawal Modifies Prion Protein Expression in Rat Hippocampus

Prion protein scrapie and the normal cellular prion protein

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