Copper Binding Regulates Cellular Prion Protein Function

Nguyen, Xuan T. A.; Tran, Thanh Hoa; Cojoc, D.; Legname, Giuseppe

doi:10.1007/s12035-019-1510-9

Cited by 34 publications

(26 citation statements)

References 38 publications

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“…It is believed that PrP C participates in many physiological processes, including signal transduction, maintaining copper or zinc homeostasis, and acting as a receptor (Halliday et al, 2014; Quek and Hill, 2017; Tamguney and Korczyn, 2018). The crucial role of copper-binding sites in maintaining the neuritogenesis function in PrP C has been proven (Nguyen et al, 2019). The central causative event in neurodegeneration is the conversion of the normal form PrP C into a protease-resistant, disease-associated form PrP Sc , which is known as templated conformation change.…”

Section: Prion Diseases and Prion-like Mechanismmentioning

confidence: 99%

Prion-Like Mechanisms in Parkinson’s Disease

Gao

Wang

et al. 2019

Front. Neurosci.

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Formation and aggregation of misfolded proteins in the central nervous system (CNS) is a key hallmark of several age-related neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). These diseases share key biophysical and biochemical characteristics with prion diseases. It is believed that PD is characterized by abnormal protein aggregation, mainly that of α-synuclein (α-syn). Of particular importance, there is growing evidence indicating that abnormal α-syn can spread to neighboring brain regions and cause aggregation of endogenous α-syn in these regions as seeds, in a “prion-like” manner. Abundant studies in vitro and in vivo have shown that α-syn goes through a templated conformational change, propagates from the original region to neighboring regions, and eventually cause neuron degeneration in the substantia nigra and striatum. The objective of this review is to summarize the mechanisms involved in the aggregation of abnormal intracellular α-syn and its subsequent cell-to-cell transmission. According to these findings, we look forward to effective therapeutic perspectives that can block the progression of neurodegenerative diseases.

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Section: Prion Diseases and Prion-like Mechanismmentioning

confidence: 99%

Prion-Like Mechanisms in Parkinson’s Disease

Gao

Wang

et al. 2019

Front. Neurosci.

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“…Huang et al found that PrP C binds to α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type and/or NMDA-type glutamate receptors and affects their function in a Cu-dependent manner [70]. Cu reportedly also affects the expression and cellular trafficking of PrP C [71], as well as physiological functions such as neurite outgrowth [72].…”

Section: Prion Diseases and Neurometalsmentioning

confidence: 99%

Amyloids: Regulators of Metal Homeostasis in the Synapse

2020

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Conformational changes in amyloidogenic proteins, such as β-amyloid protein, prion proteins, and α-synuclein, play a critical role in the pathogenesis of numerous neurodegenerative diseases, including Alzheimer’s disease, prion disease, and Lewy body disease. The disease-associated proteins possess several common characteristics, including the ability to form amyloid oligomers with β-pleated sheet structure, as well as cytotoxicity, although they differ in amino acid sequence. Interestingly, these amyloidogenic proteins all possess the ability to bind trace metals, can regulate metal homeostasis, and are co-localized at the synapse, where metals are abundantly present. In this review, we discuss the physiological roles of these amyloidogenic proteins in metal homeostasis, and we propose hypothetical models of their pathogenetic role in the neurodegenerative process as the loss of normal metal regulatory functions of amyloidogenic proteins. Notably, these amyloidogenic proteins have the capacity to form Ca2+-permeable pores in membranes, suggestive of a toxic gain of function. Therefore, we focus on their potential role in the disruption of Ca2+ homeostasis in amyloid-associated neurodegenerative diseases.

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“…Membrane-anchored PrP C presents the ability to bind extracellular Cu 2+ ions at the highly conserved octapeptide repeats (OR) region of the protein near the N-terminus [71][72][73][74]. This PrP C -Cu 2+ interaction provides antioxidant properties to the protein as demonstrated by reducing copper-mediated oxidative stress [75].…”

Section: Antioxidant Activitymentioning

confidence: 99%

The Quest for Cellular Prion Protein Functions in the Aged and Neurodegenerating Brain

Gavı́n

Lidón

Ferrer

et al. 2020

Cells

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Cellular (also termed ‘natural’) prion protein has been extensively studied for many years for its pathogenic role in prionopathies after misfolding. However, neuroprotective properties of the protein have been demonstrated under various scenarios. In this line, the involvement of the cellular prion protein in neurodegenerative diseases other than prionopathies continues to be widely debated by the scientific community. In fact, studies on knock-out mice show a vast range of physiological functions for the protein that can be supported by its ability as a cell surface scaffold protein. In this review, we first summarize the most commonly described roles of cellular prion protein in neuroprotection, including antioxidant and antiapoptotic activities and modulation of glutamate receptors. Second, in light of recently described interaction between cellular prion protein and some amyloid misfolded proteins, we will also discuss the molecular mechanisms potentially involved in protection against neurodegeneration in pathologies such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.

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Copper Binding Regulates Cellular Prion Protein Function

Cited by 34 publications

References 38 publications

Prion-Like Mechanisms in Parkinson’s Disease

Prion-Like Mechanisms in Parkinson’s Disease

Amyloids: Regulators of Metal Homeostasis in the Synapse

The Quest for Cellular Prion Protein Functions in the Aged and Neurodegenerating Brain

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