Prion protein attenuates excitotoxicity by inhibiting NMDA receptors

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Prion protein attenuates excitotoxicity by inhibiting NMDA receptors

It is well established that misfolded forms of cellular prion protein (PrP [PrP(C)]) are crucial in the genesis and progression of transmissible spongiform encephalitis, whereas the function of native PrP(C) remains incompletely understood. To determine the physiological role of PrP(C), we examine the neurophysiological properties of hippocampal neurons isolated from PrP-null mice. We show that...

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Cellular prion protein and NMDA receptor modulation: protecting against excitotoxicity

Although it is well established that misfolding of the cellular prion protein (PrP(C)) into the β-sheet-rich, aggregated scrapie conformation (PrP(Sc)) causes a variety of transmissible spongiform encephalopathies (TSEs), the physiological roles of PrP(C) are still incompletely understood. There is accumulating evidence describing the roles of PrP(C) in neurodegeneration and neuroinflammation. ...

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Distinct roles of synaptic and extrasynaptic NMDA receptors in excitotoxicity.

Excitatory synaptic activity governs excitotoxicity and modulates the distribution of NMDA receptors (NMDARs) among synaptic and extrasynaptic sites of central neurons. We investigated whether NMDAR localization was functionally linked to excitotoxicity by perturbing F-actin, a cytoskeletal protein that participates in targeting synaptic NMDARs in dendritic spines. Depolymerizing F-actin did no...

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A mutant prion protein sensitizes neurons to glutamate-induced excitotoxicity.

Growing evidence suggests that a physiological activity of the cellular prion protein (PrP(C)) plays a crucial role in several neurodegenerative disorders, including prion and Alzheimer's diseases. However, how the functional activity of PrP(C) is subverted to deliver neurotoxic signals remains uncertain. Transgenic (Tg) mice expressing PrP with a deletion of residues 105-125 in the central reg...

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Neuroprotection, excitotoxicity and NMDA antagonists.

PURPOSE To analyze the main aspects of neuroprotection and excitotoxicity. DISCUSSION This is a significant theory on the pathophysiology of cerebral ischemia; it is based on the release of excitatory aminoacid (EAA), mainly glutamate. The sequence starts with a decrease of the blood flow and ends in neuronal death. The main stages of this reaction are herein presented and discussed. An in de...

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ژورنال

عنوان ژورنال: Journal of Cell Biology

سال: 2009

ISSN: 1540-8140,0021-9525

DOI: 10.1083/jcb.20071100220090522c