Molecular and cellular mechanisms of excitotoxic neuronal death

Wang, Yan; Qin, Zheng‐Hong

doi:10.1007/s10495-010-0481-0

Cited by 366 publications

(257 citation statements)

References 274 publications

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“…Excitoxicity is a process in which N-methyl-D-aspartate (NMDA) receptor hyperactivation results in toxic changes in a neuron that occur by a variety of mechanisms [75]. There is extensive evidence from both human and rodent studies to suggest that excitotoxic insult is a component of neurodegeneration in HD, particularly in the MSNs of the striatum.…”

Section: Potential Contributions Of Altered Neuronal Function To Neurmentioning

confidence: 99%

The Role for Alterations in Neuronal Activity in the Pathogenesis of Polyglutamine Repeat Disorders

Chopra

Shakkottai

2014

Neurotherapeutics

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Polyglutamine diseases are a class of neurodegenerative diseases that share an expansion of a glutamineencoding CAG tract in the respective disease genes as a central hallmark. In all of these diseases there is progressive degeneration in a select subset of neurons, and the mechanisms behind this degeneration remain unclear. Emerging evidence from animal models of disease has identified abnormalities in synaptic signaling and intrinsic excitability in affected neurons, which coincide with the onset of symptoms and precede apparent neuropathology. The appearance of these early changes suggests that altered neuronal activity might be an important component of network dysfunction and that these alterations in network physiology could contribute to symptoms of disease. Here we review abnormalities in neuronal function that have been identified in both animal models and patients, and highlight ways in which these changes in neuronal activity may contribute to disease symptoms. We then review the literature supporting an emerging role for abnormalities in neuronal activity as a driver of neurodegeneration. Finally, we identify common themes that emerge from studies of neuronal dysfunction in polyglutamine disease.

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Section: Potential Contributions Of Altered Neuronal Function To Neurmentioning

confidence: 99%

The Role for Alterations in Neuronal Activity in the Pathogenesis of Polyglutamine Repeat Disorders

Chopra

Shakkottai

2014

Neurotherapeutics

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“…The detailed mechanism is not well understood; however, some possible hypotheses have been proposed (Dong et al, 2009;Lau and Tymianski, 2010;Wang and Qin, 2010). The important hypothetical steps of glutamate excitotoxicity are: (1) activation of ionotropic and metabotropic glutamate receptors, and subsequent membrane depolarisation; (2) excess ion infl ux, including calcium via membrane channels and/or ER localised channels; (3) oxidative stress elicited by aberrant production of reactive oxygen species (ROS); and (4) mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity

et al. 2016

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-Citrinin, a natural mycotoxin that is found in fermented foods, is known as a cytotoxin and nephrotoxin. Exposure to high doses of citrinin result in apoptosis; however, the effects of low doses are not fully understood. Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders including stroke, trauma and other neurodegenerative diseases. Here, we show the neuroprotective effect of low doses of citrinin against glutamate-induced excitotoxicity. We examined the effect of citrinin exposure on glutamate-induced cell death in cultured rat cortical neurons under two conditions: simultaneous treatment with citrinin 0.1 to 1,000 nM and glutamate (30 μM) for 1, 3 hr; the same simultaneous treatment for 3 hr after pretreatment with citrinin for 21 hr. Both the MTT and immunocytochemical assay showed significant neuroprotective effects at several doses and exposure times tested. All concentrations of citrinin tested showed no remarkable cell death following 14-day exposure, and no marked alterations to synapses. These data suggest that low doses of citrinin can be used as a neuroprotective agent against glutamate-induced excitotoxicity without additional harmful cellular alterations.

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“…As a consequence, disturbance in glutamatergic activity may underlie many psychological and neurodegenerative disorders including AD, HD, ALS, AIDS dementia complex, and PD [260]. Excessive stimulation of glutamate receptors can have numerous detrimental effects such as Ca 2+ homeostasis dysfunction, increased NO production, activation of proteases, an increase in cytotoxic transcription factors, and increased free radicals [261]. Glutamate receptor over-stimulation leads to excessive infl ux of Ca 2+ (and Na + ) through glutamate receptor-gated ion channels, followed passively by movements swelling, and plasma membrane failure leads to necrosis [262].…”

Section: Glutamate In Pdmentioning

confidence: 99%

Restoration of Mitochondrial Dysfunction in 6-Hydroxydopamine Induced Parkinson’s disease: a Complete Review

Mehan¹,

Kaur²,

Dudi³

et al. 2017

Open J Parkinsons Dis Treatm

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Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by neuronal cell death in the specifi c brain region like basal ganglia, cerebral cortex and hippocampus. Symptoms associated with PD patients are rigidity, akathesia, tremor, postural imbalance, cognitive and memory dysfunctions. Pathological hallmarks are dopaminergic neuronal degeneration, neuro-infl ammation, oxidative stress, free radical generation. In the typical Parkinson's disease model, 6-Hydroxydopamine (6-OHDA) is delivered unilaterally by stereotactic injection into the SNc (substantia nigra pars-compacta) or the striatum mimics the PD symptoms. In addition, it has been shown that 6-OHDA is toxic to complex I & IV of the mitochondrial respiratory chain, leading to subsequent respiratory inhibition and further processed ATP depletion, oxidative stress and neuro-infl ammation. Forskolin (FSK), a diterpene natural plant phytochemical obtained from (Coleus Forskohli), a potent direct activator of adenyl cyclase (AC) enzyme which further activates cAMP/PK A /CREB pathway. FSK mediated activation of AC/cAMP/PK A / CREB pathway is responsible for various neuroprotective mechanisms Based on important and versatile role of FSK, the present study has been designed to investigate the role of cAMP mediated CREB activation in 6-hydroxydopamine induced mitochondrial associated neurotoxicity in rats. Further the studies are extended to understand the disease pathogenesis and to investigate and discuss the various possible central mechanisms involved in the effect of such targets using behavioral paradigm and biochemical markers of neurodegeneration.

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Molecular and cellular mechanisms of excitotoxic neuronal death

Cited by 366 publications

References 274 publications

The Role for Alterations in Neuronal Activity in the Pathogenesis of Polyglutamine Repeat Disorders

The Role for Alterations in Neuronal Activity in the Pathogenesis of Polyglutamine Repeat Disorders

Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity

Restoration of Mitochondrial Dysfunction in 6-Hydroxydopamine Induced Parkinson’s disease: a Complete Review

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