scholarly journals Mutation of copper binding sites on cellular prion protein abolishes its inhibitory action on NMDA receptors in mouse hippocampal neurons

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sun Huang ◽  
Stefanie A. Black ◽  
Junting Huang ◽  
Peter K. Stys ◽  
Gerald W. Zamponi
Keyword(s):  
Nmda Receptor ◽  
Prion Protein ◽  
Binding Sites ◽  
Hippocampal Neurons ◽  
Primary Cultures ◽  
Cellular Prion Protein ◽  
Null Mouse ◽  
Dependent Manner ◽  
Copper Binding ◽  
Copper Binding Sites

AbstractWe have previously reported that cellular prion protein (PrPC) can down-regulate NMDA receptor activity and in a copper dependent manner. Here, we employed AAV9 to introduce murine cellular prion protein into mouse hippocampal neurons in primary cultures from PrP null mice to determine the role of the six copper binding motifs located within the N-terminal domain of PrPC. The results demonstrate that viral expression of wild type PrPC lowers NMDAR activity in PrP null mouse hippocampal neurons by reducing the magnitude of non-desensitizing currents. Elimination of the last two copper binding sites alone, or in combination with the remaining four attenuates this protective effect. Thus our data suggest that copper ion interactions with specific binding sites on PrPC are critical for PrPC dependent modulation of NMDA receptor function.

Cellular prion protein mediates laminin-dependent neurite outgrowth in primary cultures of rat and mouse hippocampal neurons

2000 ◽  
Vol 21 ◽  
pp. 52
Author(s):  
Orestes V. Forlenza ◽  
Silvio M. Zanata ◽  
Edgard Graner ◽  
Adriana F. Mercadante ◽  
Vilma R. Martins ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Prion Protein ◽  
Hippocampal Neurons ◽  
Primary Cultures ◽  
Cellular Prion Protein

scholarly journals Prion protein attenuates excitotoxicity by inhibiting NMDA receptors

2008 ◽  
Vol 181 (3) ◽  
pp. 551-565 ◽  
Author(s):  
Houman Khosravani ◽  
Yunfeng Zhang ◽  
Shigeki Tsutsui ◽  
Shahid Hameed ◽  
Christophe Altier ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Prion Protein ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Physiological Role ◽  
Cellular Prion Protein ◽  
Glutamate Excitotoxicity ◽  
Null Mouse

It is well established that misfolded forms of cellular prion protein (PrP [PrPC]) are crucial in the genesis and progression of transmissible spongiform encephalitis, whereas the function of native PrPC remains incompletely understood. To determine the physiological role of PrPC, we examine the neurophysiological properties of hippocampal neurons isolated from PrP-null mice. We show that PrP-null mouse neurons exhibit enhanced and drastically prolonged N-methyl-d-aspartate (NMDA)–evoked currents as a result of a functional upregulation of NMDA receptors (NMDARs) containing NR2D subunits. These effects are phenocopied by RNA interference and are rescued upon the overexpression of exogenous PrPC. The enhanced NMDAR activity results in an increase in neuronal excitability as well as enhanced glutamate excitotoxicity both in vitro and in vivo. Thus, native PrPC mediates an important neuroprotective role by virtue of its ability to inhibit NR2D subunits.

scholarly journals Molecular Features of the Copper Binding Sites in the Octarepeat Domain of the Prion Protein†

Biochemistry ◽  
2002 ◽  
Vol 41 (12) ◽  
pp. 3991-4001 ◽  
Author(s):  
Colin S. Burns ◽  
Eliah Aronoff-Spencer ◽  
Christine M. Dunham ◽  
Paula Lario ◽  
Nikolai I. Avdievich ◽  
...  
Keyword(s):  
Prion Protein ◽  
Binding Sites ◽  
Copper Binding ◽  
Molecular Features ◽  
Copper Binding Sites

Copper binding sites in the C‐terminal domain of mouse prion protein: A hybrid (QM/MM) molecular dynamics study

2008 ◽  
Vol 70 (3) ◽  
pp. 1084-1098 ◽  
Author(s):  
Maria Carola Colombo ◽  
Joost VandeVondele ◽  
Sabine Van Doorslaer ◽  
Alessandro Laio ◽  
Leonardo Guidoni ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Prion Protein ◽  
Binding Sites ◽  
Protein A ◽  
Copper Binding ◽  
Terminal Domain ◽  
Copper Binding Sites

Determination of copper binding sites in peptides containing basic residues: a combined experimental and theoretical study

2001 ◽  
Vol 204 (1-3) ◽  
pp. 31-46 ◽  
Author(s):  
Brian K. Bluhm ◽  
Sharon J. Shields ◽  
Craig A. Bayse ◽  
Michael B. Hall ◽  
David H. Russell
Keyword(s):  
Binding Sites ◽  
Theoretical Study ◽  
Copper Binding ◽  
Determination Of Copper ◽  
Copper Binding Sites

Copper Binding Regulates Cellular Prion Protein Function

2019 ◽  
Vol 56 (9) ◽  
pp. 6121-6133 ◽  
Author(s):  
Xuan T. A. Nguyen ◽  
Thanh Hoa Tran ◽  
Dan Cojoc ◽  
Giuseppe Legname
Keyword(s):  
Prion Protein ◽  
Protein Function ◽  
Cellular Prion Protein ◽  
Copper Binding

scholarly journals Protective Effects of Scolopendra Water Extract on Trimethyltin-Induced Hippocampal Neurodegeneration and Seizures in Mice

2019 ◽  
Vol 9 (12) ◽  
pp. 369
Author(s):  
Yun-Soo Seo ◽  
Mary Jasmin Ang ◽  
Byeong Cheol Moon ◽  
Hyo Seon Kim ◽  
Goya Choi ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Primary Cultures ◽  
Water Extract ◽  
Model Systems ◽  
Inflammatory Factor ◽  
Dependent Manner ◽  
Protective Effects ◽  
Cell Degeneration

Trimethyltin (TMT) is an organotin compound with potent neurotoxic action characterized by neuronal degeneration in the hippocampus. This study evaluated the protective effects of a Scolopendra water extract (SWE) against TMT intoxication in hippocampal neurons, using both in vitro and in vivo model systems. Specifically, we examined the actions of SWE on TMT- (5 mM) induced cytotoxicity in primary cultures of mouse hippocampal neurons (7 days in vitro) and the effects of SWE on hippocampal degeneration in adult TMT- (2.6 mg/kg, intraperitoneal) treated C57BL/6 mice. We found that SWE pretreatment (0–100 μg/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, as determined by lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that perioral administration of SWE (5 mg/kg), from −6 to 0 days before TMT injection, significantly attenuated hippocampal cell degeneration and seizures in adult mice. Furthermore, quantitative analysis of Iba-1 (Allograft inflammatory factor 1)- and GFAP (Glial fibrillary acidic protein)-immunostained cells revealed a significant reduction in the levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus (DG) of mice treated with SWE prior to TMT injection. These data indicated that SWE pretreatment significantly protected the hippocampus against the massive activation of microglia and astrocytes elicited by TMT. In addition, our data showed that the SWE-induced reduction of immune cell activation was linked to a significant reduction in cell death and a significant improvement in TMT-induced seizure behavior. Thus, we conclude that SWE ameliorated the detrimental effects of TMT toxicity on hippocampal neurons, both in vivo and in vitro. Altogether, our findings hint at a promising pharmacotherapeutic use of SWE in hippocampal degeneration and dysfunction.

Scaffolded amino acids as a close structural mimic of type-3 copper binding sites

2007 ◽  
pp. 4895 ◽  
Author(s):  
H. Bauke Albada ◽  
Fouad Soulimani ◽  
Bert M. Weckhuysen ◽  
Rob M. J. Liskamp
Keyword(s):  
Amino Acids ◽  
Binding Sites ◽  
Copper Binding ◽  
Type 3 ◽  
Copper Binding Sites

scholarly journals Interactions between Copper-binding Sites Determine the Redox Status and Conformation of the Regulatory N-terminal Domain of ATP7B

2009 ◽  
Vol 285 (9) ◽  
pp. 6327-6336 ◽  
Author(s):  
Erik S. LeShane ◽  
Ujwal Shinde ◽  
Joel M. Walker ◽  
Amanda N. Barry ◽  
Ninian J. Blackburn ◽  
...  
Keyword(s):  
Binding Sites ◽  
Redox Status ◽  
Copper Binding ◽  
Terminal Domain ◽  
Copper Binding Sites
Sign in / Sign up

Export Citation Format

Share Document