The Editorial for this Special Issue
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EDITORIAL
The Editorial for this Special Issue Donald DeGracia & Bingren Hu
Received: 21 October 2013 / Accepted: 23 October 2013 / Published online: 8 November 2013 # Springer Science+Business Media New York 2013
This special issue of Translational Stroke Research focusing on “Protein Misfolding and Organelle Stress after Brain Ischemia” grew, in part, from a symposium presented at the XXVth International Symposium on Cerebral Blood Flow, Metabolism and Function held in Barcelona, Spain, in May of 2011. Both that symposium and this special issue seek to raise awareness in the field of how brain ischemia as a multifactorial condition affects all subcellular organelles. For some time, the idea has dominated the field that ischemia-induced neuronal death was due mainly to activation of pro-death pathways such as free radical production or apoptosis or due merely to a single event such as the endoplasmic reticulum (ER) or mitochondrial failure. While these clearly are important aspects of ischemic damage, the latest studies suggest that brain ischemia leads to protein misfolding and deposition, and multiple organelle stress. To survive this nasty environment, postischemic neurons must cope with repair and eliminate irreparable damaged organelles and toxic materials by upregulation of cellular defense systems such as molecular chaperones and cellular degradation pathways. Furthermore, excessive cellular digestion might also contribute to neuronal damage. Growing evidence supports that many established ischemic damaging events converge to generate multiple organelle damage. These detrimental events include protein misfolding and aggregation, synaptic dysfunction, translational arrest, ER stress, mitochondrial dysfunction, acidosis, reactive oxygen species (ROS), dysfunction of protein quality control systems, and impairment of protein degradation pathways. Collectively, these lead to dramatic deposition of misfolded proteins on Guest editors: Donald DeGracia and Bingren Hu D. DeGracia : B. Hu (*) University of Maryland School of Medicine, Baltimore, MD, USA e-mail: [email protected]
multiple organelle membranes. Postischemic neurons respond to overload of misfolded proteins by (1) shutting off protein synthesis to reduce the load of the major cellular unfolded nascent polypeptides, (2) expression of molecular chaperones that prevent misfolded protein-induced toxicity and to repair organelle damage, and (3) upregulating protein degradation pathways for eliminating damaged organelles. The multiple organelle damage occurs mainly in neurons that are destined to die such as CA1 neurons after transient cerebral ischemia and penumbral neurons after focal brain ischemia [1]. There are other important aspects of brain ischemia research. These may include stroke biomarker discovery, inflammatory reaction, immune responses, autoantibodies, stem cell-based therapy, antibody therapy, personalized medicine, stroke prevention, and long-term stroke recovery. These interesting topics can be found in Translational Stroke Research (e.g.,
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