Delineating the molecular pathways underlying seizure-induced neuronal death may yield novel strategies for brain protection against prolonged or repetitive seizures. Glutamate-mediated excitotoxicity and necrosis is a primary contributing mechanism but seizures also activate programmed (apoptotic) cell death pathways. Apoptosis signalling pathways are typically initiated following perturbation of intracellular organelle function (intrinsic pathway) or by activated cell-surface-expressed death receptors (extrinsic pathway), with signalling cascades orchestrated in part by the Bcl-2 and caspase gene families. In this review, evidence for these pathways from experimental seizure modelling and clinical material from patients with intractable temporal lobe epilepsy is examined. Seizures cause mitochondrial dysfunction and activate intrinsic pathway components including pro-apoptotic Bcl-2 family proteins and caspases, processes that may be partly calcium-induced. The ER (endoplasmic reticulum) has emerged as a major intrinsic pathway trigger for apoptosis and its function may also be compromised following seizures and in epilepsy. The extrinsic, death-receptor-dependent pathway is also rapidly engaged following experimental seizures and in patient brain, supporting a previously unexpected apical role for a calcium-independent pathway. When considered alongside emerging functions of apoptosis-regulatory proteins in non-cell-death processes, including regulating intracellular calcium release and neuronal (re)structuring, apoptosis signalling pathways can be viewed as an important developing focus of research into how to obviate the deleterious impact of seizures on the brain.
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April 2007
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Conference Article|
March 20 2007
Apoptosis signalling pathways in seizure-induced neuronal death and epilepsy
D.C. Henshall
D.C. Henshall
1
1Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
1email [email protected]
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Publisher: Portland Press Ltd
Received:
August 14 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2007 The Biochemical Society
2007
Biochem Soc Trans (2007) 35 (2): 421–423.
Article history
Received:
August 14 2007
Citation
D.C. Henshall; Apoptosis signalling pathways in seizure-induced neuronal death and epilepsy. Biochem Soc Trans 1 April 2007; 35 (2): 421–423. doi: https://doi.org/10.1042/BST0350421
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