Original scientific paper
https://doi.org/10.3325/cmj.2019.60.121
Necroptosis is one of the modalities of cell death accompanying ischemic brain stroke: from pathogenesis to therapeutic possibilities
Valentina Hribljan
; Laboratory for Stem Cells, Department for Neurogenetics,Medical Genetics and Regenerative Neuroscience, Croatian Institutefor Brain Research, University ofZagreb School of Medicine, Zagreb,Croatia
Damir Lisjak
; Laboratory for Stem Cells, Department for Neurogenetics,Medical Genetics and Regenerative Neuroscience, Croatian Institutefor Brain Research, University ofZagreb School of Medicine, Zagreb,Croatia
Dražen Juraj Petrović
; Laboratory for Stem Cells, Department for Neurogenetics,Medical Genetics and Regenerative Neuroscience, Croatian Institutefor Brain Research, University ofZagreb School of Medicine, Zagreb,Croatia
Dinko Mitrečić
; Laboratory for Stem Cells, Department for Neurogenetics,Medical Genetics and Regenerative Neuroscience, Croatian Institutefor Brain Research, University ofZagreb School of Medicine, Zagreb,Croatia
Abstract
Due to very limited therapeutic options, ischemic brain injury
is one of the leading causes of death and lifelong disability
worldwide, which imposes enormous public health
burden. One of the main events occurring with ischemic
brain stroke is cell death. Necroptosis is a type of cell death
described as a regulated necrosis characterized by cell
membrane disruption mediated by phosphorylated mixed
lineage kinase like protein (MLKL). It can be triggered by
activation of death receptors (eg, FAS, TNFR1), which lead
to receptor-interacting serine/threonine-protein kinase 3
(RIPK3) activation by RIPK1 in the absence of active caspase-
8. Here, we review articles that have reported that
necroptosis significantly contributes to negative events
occurring with the ischemic brain stroke, and that its inhibition
is protective both in vitro and in vivo. We also review
articles describing positive effects obtained by reducing
necroptosis, including the reduction of infarct volume
and improved functional recovery in animal models. Since
necroptosis is characterized by cell content leakage and
subsequent inflammation, in addition to reducing cell
death, inhibition of necroptosis in ischemic brain stroke
also reduces some inflammatory cytokines. By comparing
various approaches in inhibition of necroptosis, we analyze
the achieved effects from the perspective of controlling
necroptosis as a part of future therapeutic interventions in
brain ischemia.
Keywords
Hrčak ID:
239737
URI
Publication date:
15.4.2019.
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