Journal ArticleDOI
Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death.
Rita Sattler,Michael Tymianski +1 more
TLDR
The present review is aimed at summarizing the molecular mechanisms of NMDA receptor and AMPA/kainate receptor-mediated excitotoxic neuronal cell death.Abstract:
Excitotoxicity is one of the most extensively studied processes of neuronal cell death, and plays an important role in many central nervous system (CNS) diseases, including CNS ischemia, trauma, and neurodegenerative disorders. First described by Olney, excitotoxicity was later characterized as an excessive synaptic release of glutamate, which in turn activates postsynaptic glutamate receptors. While almost every glutamate receptor subtype has been implicated in mediating excitotoxic cell death, it is generally accepted that the N-methyl-D-aspartate (NMDA) subtypes play a major role, mainly owing to their high calcium (Ca2+) permeability. However, other glutamate receptor subtypes such as 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionate (AMPA) or kainate receptors have also been attributed a critical role in mediating excitotoxic neuronal cell death. Although the molecular basis of glutamate toxicity is uncertain, there is general agreement that it is in large part Ca2+-dependent. The present review is aimed at summarizing the molecular mechanisms of NMDA receptor and AMPA/kainate receptor-mediated excitotoxic neuronal cell death.read more
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Calcium, ATP, and ROS: a mitochondrial love-hate triangle
TL;DR: A "two-hit" hypothesis is developed, in which Ca(2+) plus another pathological stimulus can bring about mitochondrial dysfunction, and the delicate balance between the positive and negative effects of Ca( 2+) and the signaling events that perturb this balance is highlighted.
Journal ArticleDOI
Regulated necrosis: the expanding network of non-apoptotic cell death pathways
Tom Vanden Berghe,Andreas Linkermann,Sandrine Jouan-Lanhouet,Henning Walczak,Peter Vandenabeele +4 more
TL;DR: Elucidating how these pathways of regulated necrosis are interconnected at the molecular level should enable this process to be therapeutically targeted.
Journal ArticleDOI
CB1 cannabinoid receptors and on-demand defense against excitotoxicity.
Giovanni Marsicano,Sharon Goodenough,Sharon Goodenough,Krisztina Monory,Heike Hermann,Matthias Eder,Astrid Cannich,Shahnaz Christina Azad,Maria Grazia Cascio,Silvia Ortega Gutierrez,Mario van der Stelt,María L. López-Rodríguez,Emilio Casanova,Günther Schütz,Walter Zieglgänsberger,Vincenzo Di Marzo,Christian Behl,Beat Lutz +17 more
TL;DR: The endogenous cannabinoid system provides on-demand protection against acute excitotoxicity in central nervous system neurons and could not be triggered in mutant mice.
Journal ArticleDOI
Necrotic death as a cell fate
Wei-Xing Zong,Craig B. Thompson +1 more
TL;DR: Evidence suggests that a cell can initiate its own demise by necrosis in a manner that initiates both inflammatory and/or reparative responses in the host, and may serve to maintain tissue and organismal integrity.
Journal ArticleDOI
Retinal ischemia: mechanisms of damage and potential therapeutic strategies.
TL;DR: Given the increasing understanding of the events involved in ischemic neuronal injury, it is hoped that clinically effective treatments for retinal ischemia will soon be available.
References
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