Journal Article10.1007/S10495-010-0481-0
Molecular and cellular mechanisms of excitotoxic neuronal death
Yan Wang,Zheng-Hong Qin +1 more
419
TL;DR: The current understanding of the molecular and cellular mechanisms of excitotoxicity and their roles in the pathogenesis of diseases of the central nervous system are discussed.
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Abstract: Glutamate receptor-mediated excitatory neurotransmission plays a key role in neural development, differentiation and synaptic plasticity. However, excessive stimulation of glutamate receptors induces neurotoxicity, a process that has been defined as excitotoxicity. Excitotoxicity is considered to be a major mechanism of cell death in a number of central nervous system diseases including stroke, brain trauma, epilepsy and chronic neurodegenerative disorders. Unfortunately clinical trials with glutamate receptor antagonists, that would logically prevent the effects of excessive receptor activation, have been associated with untoward side effects or little clinical benefit. Therefore, uncovering molecular pathways involved in excitotoxic neuronal death is of critical importance to future development of clinical treatment of many neurodegenerative disorders where excitotoxicity has been implicated. This review discusses the current understanding of the molecular and cellular mechanisms of excitotoxicity and their roles in the pathogenesis of diseases of the central nervous system.
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Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release
TL;DR: Astrocytes contribute to glutamate homeostasis in the CNS, by maintaining the balance between their opposing functions of glutamate uptake and release, and the main features of glutamate metabolism and glutamate excitotoxicity and its implication in CNS diseases are reviewed.
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Role of Excitatory Amino Acid Transporter‐2 (EAAT2) and glutamate in neurodegeneration: Opportunities for developing novel therapeutics
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TL;DR: The potential utility of the EAAT2 promoter is emphasized for developing both low and high throughput screening assays to identify novel small molecule regulators of glutamate transport with potential to ameliorate pathological changes occurring during and causing neurodegeneration.
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Researching glutamate - induced cytotoxicity in different cell lines: a comparative/collective analysis/study
TL;DR: In the greatest majority of the cell lines ionotropic glutamate receptors are present, co-existing to CySS/glutamate antiporters and metabotropic glutamate receptor, supporting the assumption that excitotoxicity effect in these cells is accumulative.
References
Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases
Michael T. Lin,M. Flint Beal +1 more
TL;DR: Treatments targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria hold great promise in ageing-related neurodegenerative diseases.
6.2K
Cell Death: Critical Control Points
TL;DR: The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics.
5K
Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation
TL;DR: Experiments with PC12 cells suggest that the duration of ERK activation is critical for cell signaling decisions, and the extracellular signal-regulated kinase (ERK-regulated) MAPK pathway may be sufficient for these cellular responses.
4.8K
Cloned Glutamate Receptors
TL;DR: The application of molecular cloning technology to the study of the glutamate receptor system has led to an explosion of knowledge about the structure, expression, and function of this most important fast excitatory transmitter system in the mammalian brain.
4.2K
Oxidative stress, glutamate, and neurodegenerative disorders
TL;DR: Two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain.
4K