ORCID Profile
0000-0001-6237-9632
Current Organisation
Royal College of Surgeons in Ireland
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Publisher: Elsevier BV
Date: 09-2016
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 15-05-2023
Publisher: Springer Science and Business Media LLC
Date: 25-09-2009
DOI: 10.1038/CDD.2009.134
Publisher: Springer Science and Business Media LLC
Date: 27-07-2020
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2023
Publisher: Wiley
Date: 30-07-2010
DOI: 10.1111/J.1471-4159.2010.06909.X
Abstract: Prolonged seizures activate members of the Bcl-2 homology domain 3-only sub-group of the Bcl-2 protein family, which are essential for initiation of apoptosis signaling. Bid is a potent pro-apoptotic Bcl-2 homology domain 3-only protein, which upon proteolytic activation translocates to mitochondria to promote activation of the Bax/Bak sub-group of the pro-apoptotic Bcl-2 family and thereby contributes to release of apoptogenic molecules, such as cytochrome c and possibly apoptosis-inducing factor (AIF). Bid-deficient mice have been reported to show reduced lesion volumes after ischemia and trauma in vivo but a causal role for Bid in the setting of seizure-induced neuronal death has not been investigated. In this study, we studied Bid activation following status epilepticus in mice and compared hippoc al damage between wild-type and Bid-deficient animals. Full-length Bid was detected in normal mouse hippoc us and the cleaved (activated) p15 fragment of Bid was detected shortly after status epilepticus. Bid-deficient mice underwent equivalent electrographic seizure responses during status epilepticus as wild-type animals. Hippoc al counts of degenerating neurons and surviving neuron-specific nuclear protein-positive cells were not significantly different between wild-type and Bid-deficient mice. Additionally, nuclear translocation of AIF was not reduced in Bid-deficient compared with wild-type animals subjected to status epilepticus. The present study demonstrates that AIF is not dependent on Bid for mitochondrial release and nuclear import in this model and that while Bid is cleaved during seizure-induced neuronal death, it may be functionally redundant or even not essential.
Publisher: Springer Science and Business Media LLC
Date: 20-07-2022
DOI: 10.1038/S41582-022-00693-Y
Abstract: An increasing number of epilepsies are being attributed to variants in genes with epigenetic functions. The products of these genes include factors that regulate the structure and function of chromatin and the placing, reading and removal of epigenetic marks, as well as other epigenetic processes. In this Review, we provide an overview of the various epigenetic processes, structuring our discussion around five function-based categories: DNA methylation, histone modifications, histone-DNA crosstalk, non-coding RNAs and chromatin remodelling. We provide background information on each category, describing the general mechanism by which each process leads to altered gene expression. We also highlight key clinical and mechanistic aspects, providing ex les of genes that strongly associate with epilepsy within each class. We consider the practical applications of these findings, including tissue-based and biofluid-based diagnostics and precision medicine-based treatments. We conclude that variants in epigenetic genes are increasingly found to be causally involved in the epilepsies, with implications for disease mechanisms, treatments and diagnostics.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for David Henshall.