Loss of endoplasmic reticulum Ca2＋ homeostasis： contribution to neuronal cell death during cerebral ischemia

• Published in: Acta pharmacologica Sinica 2013-01, Vol.34 (1), p.49-59
• Main Authors: Bodalia, Ankur, Li, Hongbin, Jackson, Michael F
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Brain - blood supply; Brain - metabolism; Brain - pathology; Brain Ischemia - metabolism; Brain Ischemia - pathology; Calcium - metabolism; Cell Death; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - pathology; Endoplasmic Reticulum Stress; Homeostasis; Humans; Immunology; Internal Medicine; Medical Microbiology; Neurons - metabolism; Neurons - pathology; Pharmacology/Toxicology; Review; Unfolded Protein Response; Vaccine; 信号转导通路; 内质网; 损失; 死亡过程; 神经元损伤; 神经细胞; 脑缺血; 钙稳态
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2012.139

The loss of Ca2＋ homeostasis during cerebral ischemia is a hallmark of impending neuronal demise. Accordingly, considerable cellular resources are expended in maintaining low resting cytosolic levels of Ca2＋. These include contributions by a host of proteins involved in the sequestration and transport of Ca2＋, many of which are expressed within intracellular organelles, including lysosomes, mitochon- dria as well as the endoplasmic reticulum （ER）. Ca2＋ sequestration by the ER contributes to cytosolic Ca2＋ dynamics and homeosta- sis. Furthermore, within the ER Ca2＋ plays a central role in regulating a host of physiological processes. Conversely, impaired ER Ca2＋ homeostasis is an important trigger of pathological processes. Here we review a growing body of evidence suggesting that ER dysfunc- tion is an important factor contributing to neuronal injury and loss post-ischemia. Specifically, the contribution of the ER to cytosolic Ca2＋ elevations during ischemia will be considered, as will the signalling cascades recruited as a consequence of disrupting ER home- ostasis and function.