The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-β Oligomer Toxicity

Ostapchenko, Valeriy G.; Beraldo, Flávio H.; Mohammad, Amro H.; Xie, Yu; Hirata, Pedro H. F.; Magalhães, Ana C.; Lamour, Guillaume; Li, Hongbin; Maciejewski, Andrzej; Belrose, Jillian C.; Teixeira, Bianca Luise; Fahnestock, Margaret; Ferreira, Sérgio T.; Cashman, Neil R.; Hajj, Glaucia Noeli Maroso; Jackson, Michael; Choy, Wing Yiu; MacDonald, John F.; Martins, Vilma R.; Prado, Vânia F.; Prado, Marco A. M.

doi:10.1523/jneurosci.3214-13.2013

Cited by 75 publications

(122 citation statements)

References 78 publications

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“…PrP C expression has been reported to protect primary hippocampal neurons from staurosporine-mediated cell death, possibly through an interaction with stress-induced phosphoprotein 1 (STI1) (Lopes et al, 2005; Beraldo et al, 2010; Ostapchenko et al, 2013). STI1 is a secreted protein thought to interact with PrP C , leading to activation of the pro-survival protein kinase A (PKA) signalling pathway (Zanata et al, 2002; Lopes et al, 2005).…”

Section: Prpc Functionmentioning

confidence: 99%

Physiological Functions of the Cellular Prion Protein

Castle

Gill

2017

Front. Mol. Biosci.

168

157

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The prion protein, PrPC, is a small, cell-surface glycoprotein notable primarily for its critical role in pathogenesis of the neurodegenerative disorders known as prion diseases. A hallmark of prion diseases is the conversion of PrPC into an abnormally folded isoform, which provides a template for further pathogenic conversion of PrPC, allowing disease to spread from cell to cell and, in some circumstances, to transfer to a new host. In addition to the putative neurotoxicity caused by the misfolded form(s), loss of normal PrPC function could be an integral part of the neurodegenerative processes and, consequently, significant research efforts have been directed toward determining the physiological functions of PrPC. In this review, we first summarise important aspects of the biochemistry of PrPC before moving on to address the current understanding of the various proposed functions of the protein, including details of the underlying molecular mechanisms potentially involved in these functions. Over years of study, PrPC has been associated with a wide array of different cellular processes and many interacting partners have been suggested. However, recent studies have cast doubt on the previously well-established links between PrPC and processes such as stress-protection, copper homeostasis and neuronal excitability. Instead, the functions best-supported by the current literature include regulation of myelin maintenance and of processes linked to cellular differentiation, including proliferation, adhesion, and control of cell morphology. Intriguing connections have also been made between PrPC and the modulation of circadian rhythm, glucose homeostasis, immune function and cellular iron uptake, all of which warrant further investigation.

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Section: Prpc Functionmentioning

confidence: 99%

Physiological Functions of the Cellular Prion Protein

Castle

Gill

2017

Front. Mol. Biosci.

168

157

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“…Interaction between A␤o and PrP C is essential for development of an array of AD features, including activation of certain signaling cascades, synaptotoxicity, inhibition of long term potentiation, memory impairment, and decreased survival in mice (25,(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43). However, it was also observed that A␤o can induce AD-like phenotypes independently of PrP C in J20 mice (44) and in some in vitro studies (23,24,45).…”

mentioning

confidence: 99%

Prion-Protein-interacting Amyloid-β Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models

Kostylev¹,

Kaufman²,

Nygaard

et al. 2015

Journal of Biological Chemistry

116

132

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Background: Amyloid-␤ (A␤) oligomers are key in Alzheimer disease (AD) but are diverse and poorly characterized. Results: Multiple A␤ forms were measured across the life span of AD model mice and human AD brain. Conclusion: A␤ species interacting with prion protein were tightly linked to behavioral impairment. Significance: An A␤ oligomer subset with defined biochemical properties is present in multiple AD-relevant samples.

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“…Hop was found to prevent the binding of AβOs to PrP C , both in vitro and to mouse hippocampal neuronal PrP C in vivo (Ostapchenko et al 2013). Hop was able to prevent AβO-induced synaptic loss and neuronal death, and neurons that were haploinsufficient in Hop were more sensitive to AβO-induced death which could be rescued by treatment with recombinant Hop.…”

Section: Developmental and Protein Folding Disordersmentioning

confidence: 96%

“…Hop was able to prevent AβO-induced synaptic loss and neuronal death, and neurons that were haploinsufficient in Hop were more sensitive to AβO-induced death which could be rescued by treatment with recombinant Hop. The toxicity induced by AβOs could also be prevented by TPR2A which is the domain in Hop that interacts with PrP C (Ostapchenko et al 2013). Hop has also been implicated in other protein conformational diseases, in which various proteins are converted into a common toxic conformational state similar to β-amyloid (Wolfe et al 2013).…”

Section: Developmental and Protein Folding Disordersmentioning

confidence: 99%

Hsp70/Hsp90 Organising Protein (Hop): Beyond Interactions with Chaperones and Prion Proteins

Baindur-Hudson

Edkins

Blatch

2014

Subcellular Biochemistry

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The Hsp70/Hsp90 organising protein (Hop), also known as stress-inducible protein 1 (STI1), has received considerable attention for diverse cellular functions in both healthy and diseased states. There is extensive evidence that intracellular Hop is a co-chaperone of the major chaperones Hsp70 and Hsp90, playing an important role in the productive folding of Hsp90 client proteins. Consequently, Hop is implicated in a number of key signalling pathways, including aberrant pathways leading to cancer. However, Hop is also secreted and it is now well established that Hop also serves as a receptor for the prion protein, PrP(C). The intracellular and extracellular forms of Hop most likely represent two different isoforms, although the molecular determinants of these divergent functions are yet to be identified. There is also a growing body of research that reports the involvement of Hop in cellular activities that appear independent of either chaperones or PrP(C). While Hop has been shown to have various cellular functions, its biological function remains elusive. However, recent knockout studies in mammals suggest that Hop has an important role in embryonic development. This review provides a critical overview of the latest molecular, cellular and biological research on Hop, critically evaluating its function in healthy systems and how this function is adapted in diseases states.

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The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-β Oligomer Toxicity

Cited by 75 publications

References 78 publications

Physiological Functions of the Cellular Prion Protein

Physiological Functions of the Cellular Prion Protein

Prion-Protein-interacting Amyloid-β Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models

Hsp70/Hsp90 Organising Protein (Hop): Beyond Interactions with Chaperones and Prion Proteins

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