TY - JOUR
T1 - Autophagy in acute brain injury
T2 - Feast, famine, or folly?
AU - Smith, Craig M.
AU - Chen, Yaming
AU - Sullivan, Mara L.
AU - Kochanek, Patrick M.
AU - Clark, Robert S B
N1 - Funding Information:
This study was supported by the National Institute of Neurologic Diseases and Stroke grant R01 NS38620 , and National Institute Child Health and Human Development grants T32 HD40686 and R01 HD045968 . We would also like to thank Henry Alexander and Christina Hosler for their expert technical assistance.
Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/7
Y1 - 2011/7
N2 - In the central nervous system, increased autophagy has now been reported after traumatic brain and spinal cord injury, cerebral ischemia, intracerebral hemorrhage, and seizures. This increase in autophagy could be physiologic, converting damaged or dysfunctional proteins, lipids, and/or organelles to their amino acid and fatty acid components for recycling. On the other hand, this increase in autophagy could be supraphysiologic, perhaps consuming and eliminating functional proteins, lipids, and/or organelles as well. Whether an increase in autophagy is beneficial (feast) or detrimental (famine) in brain likely depends on both the burden of intracellular substrate targeted for autophagy and the capacity of the cell's autophagic machinery. Of course, increased autophagy observed after brain injury could also simply be an epiphenomenon (folly). These divergent possibilities have clear ramifications for designing therapeutic strategies targeting autophagy after acute brain injury and are the subject of this review. This article is part of a Special Issue entitled "Autophagy and protein degradation in neurological diseases.
AB - In the central nervous system, increased autophagy has now been reported after traumatic brain and spinal cord injury, cerebral ischemia, intracerebral hemorrhage, and seizures. This increase in autophagy could be physiologic, converting damaged or dysfunctional proteins, lipids, and/or organelles to their amino acid and fatty acid components for recycling. On the other hand, this increase in autophagy could be supraphysiologic, perhaps consuming and eliminating functional proteins, lipids, and/or organelles as well. Whether an increase in autophagy is beneficial (feast) or detrimental (famine) in brain likely depends on both the burden of intracellular substrate targeted for autophagy and the capacity of the cell's autophagic machinery. Of course, increased autophagy observed after brain injury could also simply be an epiphenomenon (folly). These divergent possibilities have clear ramifications for designing therapeutic strategies targeting autophagy after acute brain injury and are the subject of this review. This article is part of a Special Issue entitled "Autophagy and protein degradation in neurological diseases.
KW - Autophagic stress
KW - Autophagosome
KW - Hypoxia-ischemia
KW - Lipophagy
KW - Mitophagy
KW - Traumatic brain injury
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U2 - 10.1016/j.nbd.2010.09.014
DO - 10.1016/j.nbd.2010.09.014
M3 - Review article
C2 - 20883784
AN - SCOPUS:79955974998
VL - 43
SP - 52
EP - 59
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 1
ER -