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Probing the molecular mechanisms of neuronal degeneration: importance of mitochondrial dysfunction and calcineurin activation

Uchino, Hiroyuki; Kuroda, Yasuhiro; Morota, Saori LU ; Hirabayashi, Go; Ishii, Nagao; Shibasaki, Futoshi; Ikeda, Yukiho; Hansson, Magnus J. and Elmer, Eskil LU (2008) In Journal of Anesthesia 22(3). p.253-262
Abstract
Cerebral injury is a critical aspect of the management of patients in intensive care. Pathological conditions induced by cerebral ischemia, hypoxia, head trauma, and seizure activity can result in marked residual impairment of cerebral function. We have investigated the potential mechanisms leading to neuronal cell death in pathological conditions, with the aim of discovering therapeutic targets and methods to minimize neuronal damage resulting from insults directed at the central nervous system (CNS). Over the years, deeper understanding of the mechanisms of neuronal cell death has indeed evolved, enabling clinical critical care management to salvage neurons that are at the brink of degeneration and to support recovery of brain function.... (More)
Cerebral injury is a critical aspect of the management of patients in intensive care. Pathological conditions induced by cerebral ischemia, hypoxia, head trauma, and seizure activity can result in marked residual impairment of cerebral function. We have investigated the potential mechanisms leading to neuronal cell death in pathological conditions, with the aim of discovering therapeutic targets and methods to minimize neuronal damage resulting from insults directed at the central nervous system (CNS). Over the years, deeper understanding of the mechanisms of neuronal cell death has indeed evolved, enabling clinical critical care management to salvage neurons that are at the brink of degeneration and to support recovery of brain function. However, no substantial breakthrough has been achieved in the quest to develop effective pharmacological neuroprotective therapy directed at tissues of the CNS. The current situation is unacceptable, and preservation of function and protection of the brain from terminal impairment will be a vital medical issue in the twenty-first century. To achieve this goal, it is critical to clarify the key mechanisms leading to neuronal cell death. Here, we discuss the importance of the calcineurin/immunophilin signal transduction pathway and mitochondrial involvement in the detrimental chain of events leading to neuronal degeneration. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Brain, Cyclophilin, Calcineurin, Permeability transition, Mitochondria, Neuroprotection
in
Journal of Anesthesia
volume
22
issue
3
pages
253 - 262
publisher
Springer
external identifiers
  • wos:000260112500009
  • scopus:49749090449
ISSN
0913-8668
DOI
10.1007/s00540-008-0617-3
language
English
LU publication?
yes
id
384e3c11-965d-4dcb-9820-0bb44d45a060 (old id 1284917)
date added to LUP
2009-02-06 11:34:10
date last changed
2017-01-01 05:47:10
@article{384e3c11-965d-4dcb-9820-0bb44d45a060,
  abstract     = {Cerebral injury is a critical aspect of the management of patients in intensive care. Pathological conditions induced by cerebral ischemia, hypoxia, head trauma, and seizure activity can result in marked residual impairment of cerebral function. We have investigated the potential mechanisms leading to neuronal cell death in pathological conditions, with the aim of discovering therapeutic targets and methods to minimize neuronal damage resulting from insults directed at the central nervous system (CNS). Over the years, deeper understanding of the mechanisms of neuronal cell death has indeed evolved, enabling clinical critical care management to salvage neurons that are at the brink of degeneration and to support recovery of brain function. However, no substantial breakthrough has been achieved in the quest to develop effective pharmacological neuroprotective therapy directed at tissues of the CNS. The current situation is unacceptable, and preservation of function and protection of the brain from terminal impairment will be a vital medical issue in the twenty-first century. To achieve this goal, it is critical to clarify the key mechanisms leading to neuronal cell death. Here, we discuss the importance of the calcineurin/immunophilin signal transduction pathway and mitochondrial involvement in the detrimental chain of events leading to neuronal degeneration.},
  author       = {Uchino, Hiroyuki and Kuroda, Yasuhiro and Morota, Saori and Hirabayashi, Go and Ishii, Nagao and Shibasaki, Futoshi and Ikeda, Yukiho and Hansson, Magnus J. and Elmer, Eskil},
  issn         = {0913-8668},
  keyword      = {Brain,Cyclophilin,Calcineurin,Permeability transition,Mitochondria,Neuroprotection},
  language     = {eng},
  number       = {3},
  pages        = {253--262},
  publisher    = {Springer},
  series       = {Journal of Anesthesia},
  title        = {Probing the molecular mechanisms of neuronal degeneration: importance of mitochondrial dysfunction and calcineurin activation},
  url          = {http://dx.doi.org/10.1007/s00540-008-0617-3},
  volume       = {22},
  year         = {2008},
}