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Role of mitochondri...
Role of mitochondria in apoptotic and necroptotic cell death in the developing brain.
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Thornton, Claire (author)
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- Hagberg, Henrik, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institutionen för neurovetenskap och fysiologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology,Institute of Neuroscience and Physiology
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- English.
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In: Clinica chimica acta; international journal of clinical chemistry. - : Elsevier BV. - 1873-3492. ; 451:Part: A Special Issue: SI, s. 35-38
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Abstract
Subject headings
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- Hypoxic-ischemic encephalopathy induces secondary brain injury characterized by delayed energy failure. Currently, therapeutic hypothermia is the sole treatment available after severe intrapartum asphyxia in babies and acts to attenuate secondary loss of high energy phosphates improving both short- and long-term outcome. In order to develop the next generation of neuroprotective therapies, we urgently need to understand the underlying molecular mechanisms leading to cell death. Hypoxia-ischemia creates a toxic intracellular environment including accumulation of reactive oxygen/nitrosative species and intracellular calcium after the insult, inducing mitochondrial impairment. More specifically mitochondrial respiration is suppressed and calcium signaling is dysregulated. At a certain threshold, Bax-dependent mitochondrial permeabilization will occur leading to activation of caspase-dependent and apoptosis-inducing factor-dependent apoptotic cell death. In addition, hypoxia-ischemia induces inflammation, which leads to the release of TNF-α, TRAIL, TWEAK, FasL and Toll-like receptor agonists that will activate death receptors on neurons and oligodendroglia. Death receptors trigger apoptotic death via caspase-8 and necroptotic cell death through formation of the necrosome (composed of RIP1, RIP3 and MLKL), both of which converge at the mitochondria.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Perinatal brain injury
- Hypoxia–ischemia
- Mitochondria
- Apoptosis
- Necroptosis
- Necrosis
Publication and Content Type
- ref (subject category)
- art (subject category)
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