scholarly journals The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4Receptors

2011 ◽  
Vol 2011 ◽  
pp. 1-6
Author(s):  
Ramón A. Lorca ◽  
Lorena Varela-Nallar ◽  
Nibaldo C. Inestrosa ◽  
J. Pablo Huidobro-Toro
Keyword(s):  
Amino Acids ◽  
Synaptic Transmission ◽  
Prion Protein ◽  
Adenosine Triphosphate ◽  
Response Curve ◽  
Physiological Function ◽  
Cellular Prion Protein ◽  
Synaptic Activity ◽  
Receptor Subtype ◽  
Concentration Response Curve

Although the physiological function of the cellular prion protein (PrPC) remains unknown, several evidences support the notion of its role in copper homeostasis. PrPCbinds Cu2+through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+of the adenosine triphosphate (ATP)-evoked currents in the P2X4receptor subtype, highlighting a modulatory role for PrPCin synaptic transmission through regulation of Cu2+levels. Here, we study the effect of full-length PrPCin Cu2+inhibition of P2X4receptor when both are coexpressed. PrPCexpression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4receptors. However, the presence of PrPCreduces the inhibition by Cu2+of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+binding domain. Thus, our observations suggest a role for PrPCin modulating synaptic activity through binding of extracellular Cu2+.

scholarly journals Prion protein and its role in signal transduction

2013 ◽  
Vol 18 (2) ◽  
Author(s):  
Alessandro Didonna
Keyword(s):  
Signal Transduction ◽  
Prion Protein ◽  
Neurodegenerative Disorders ◽  
Physiological Function ◽  
Prion Diseases ◽  
Etiologic Agent ◽  
Cellular Prion Protein ◽  
Considerable Effort ◽  
Unique Nature ◽  
First Time

AbstractPrion diseases are a class of fatal neurodegenerative disorders that can be sporadic, genetic or iatrogenic. They are characterized by the unique nature of their etiologic agent: prions (PrPSc). A prion is an infectious protein with the ability to convert the host-encoded cellular prion protein (PrPC) into new prion molecules by acting as a template. Since Stanley B. Prusiner proposed the “protein-only” hypothesis for the first time, considerable effort has been put into defining the role played by PrPC in neurons. However, its physiological function remains unclear. This review summarizes the major findings that support the involvement of PrPC in signal transduction.

scholarly journals Expanding spectrum of prion diseases

2020 ◽  
Vol 4 (2) ◽  
pp. 155-167
Author(s):  
Jacob I. Ayers ◽  
Nick A. Paras ◽  
Stanley B. Prusiner
Keyword(s):  
Amino Acids ◽  
Nucleic Acid ◽  
Prion Protein ◽  
Prion Diseases ◽  
Lewy Body Dementia ◽  
Cellular Prion Protein ◽  
Chromosomal Gene ◽  
Scrapie Agent ◽  
Β Sheet ◽  
Translational Process

Prions were initially discovered in studies of scrapie, a transmissible neurodegenerative disease (ND) of sheep and goats thought to be caused by slow viruses. Once scrapie was transmitted to rodents, it was discovered that the scrapie pathogen resisted inactivation by procedures that modify nucleic acids. Eventually, this novel pathogen proved to be a protein of 209 amino acids, which is encoded by a chromosomal gene. After the absence of a nucleic acid within the scrapie agent was established, the mechanism of infectivity posed a conundrum and eliminated a hypothetical virus. Subsequently, the infectious scrapie prion protein (PrPSc) enriched for β-sheet was found to be generated from the cellular prion protein (PrPC) that is predominantly α-helical. The post-translational process that features in nascent prion formation involves a templated conformational change in PrPC that results in an infectious copy of PrPSc. Thus, prions are proteins that adopt alternative conformations, which are self-propagating and found in organisms ranging from yeast to humans. Prions have been found in both Alzheimer's (AD) and Parkinson's (PD) diseases. Mutations in APP and α-synuclein genes have been shown to cause familial AD and PD. Recently, AD was found to be a double prion disorder: both Aβ and tau prions feature in this ND. Increasing evidence argues for α-synuclein prions as the cause of PD, multiple system atrophy, and Lewy body dementia.

scholarly journals Insights into the physiological function of cellular prion protein

2001 ◽  
Vol 34 (5) ◽  
pp. 585-595 ◽  
Author(s):  
V.R. Martins ◽  
A.F. Mercadante ◽  
A.L.B. Cabral ◽  
A.R.O. Freitas ◽  
R.M.R.P.S. Castro
Keyword(s):  
Prion Protein ◽  
Physiological Function ◽  
Cellular Prion Protein

scholarly journals Pharmacological inactivation of the prion protein by targeting a folding intermediate

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Giovanni Spagnolli ◽  
Tania Massignan ◽  
Andrea Astolfi ◽  
Silvia Biggi ◽  
Marta Rigoli ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Surface Glycoprotein ◽  
Folding Intermediate ◽  
Biological Regulation ◽  
Cell Surface Glycoprotein ◽  
Folding Intermediates ◽  
Protein Levels ◽  
Small Molecule Ligands

AbstractRecent computational advancements in the simulation of biochemical processes allow investigating the mechanisms involved in protein regulation with realistic physics-based models, at an atomistic level of resolution. These techniques allowed us to design a drug discovery approach, named Pharmacological Protein Inactivation by Folding Intermediate Targeting (PPI-FIT), based on the rationale of negatively regulating protein levels by targeting folding intermediates. Here, PPI-FIT was tested for the first time on the cellular prion protein (PrP), a cell surface glycoprotein playing a key role in fatal and transmissible neurodegenerative pathologies known as prion diseases. We predicted the all-atom structure of an intermediate appearing along the folding pathway of PrP and identified four different small molecule ligands for this conformer, all capable of selectively lowering the load of the protein by promoting its degradation. Our data support the notion that the level of target proteins could be modulated by acting on their folding pathways, implying a previously unappreciated role for folding intermediates in the biological regulation of protein expression.

scholarly journals A new 68Ga-labeled somatostatin analog containing two iodo-amino acids for dual somatostatin receptor subtype 2 and 5 targeting

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rosalba Mansi ◽  
Karim Abid ◽  
Guillaume P. Nicolas ◽  
Luigi Del Pozzo ◽  
Eric Grouzmann ◽  
...  
Keyword(s):  
Amino Acids ◽  
Somatostatin Receptor ◽  
Somatostatin Analog ◽  
Receptor Subtype ◽  
Somatostatin Receptor Subtype 2
Sign in / Sign up

Export Citation Format

Share Document