Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0917798 (
cerebral ischemia
)
17,036
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Excessive cytosolic calcium ion (Ca(2+)) accumulation during
cerebral ischemia
triggers neuronal cell death, but the underlying mechanisms are poorly understood. Capacitive Ca(2+) entry (CCE) is a process whereby depletion of intracellular Ca(2+) stores causes the activation of plasma membrane Ca(2+) channels. In nonexcitable cells, CCE is controlled by the endoplasmic reticulum (ER)-resident Ca(2+) sensor STIM1, whereas the closely related protein
STIM2
has been proposed to regulate basal cytosolic and ER Ca(2+) concentrations and make only a minor contribution to CCE. Here, we show that
STIM2
, but not STIM1, is essential for CCE and ischemia-induced cytosolic Ca(2+) accumulation in neurons. Neurons from Stim2(-/-) mice showed significantly increased survival under hypoxic conditions compared to neurons from wild-type controls both in culture and in acute hippocampal slice preparations. In vivo, Stim2(-/-) mice were markedly protected from neurological damage in a model of focal
cerebral ischemia
. These results implicate CCE in ischemic neuronal cell death and establish
STIM2
as a critical mediator of this process.
...
PMID:STIM2 regulates capacitive Ca2+ entry in neurons and plays a key role in hypoxic neuronal cell death. 1984 59
Neuronal calcium (Ca
2+
) influx has long been ascribed mainly to voltage-gated Ca
2+
channels and glutamate receptor channels. Recent research has shown that it is also complemented by stromal interaction molecule (STIM) protein-mediated store-operated Ca
2+
entry (SOCE). SOCE is described as Ca
2+
flow into cells in response to the depletion of endoplasmic reticulum Ca
2+
stores. The present review summarizes recent studies that indicate a relationship between neuronal SOCE that is mediated by STIM1 and
STIM2
proteins and glutamate receptors under both physiological and pathological conditions, such as neurodegenerative disorders. We present evidence that the dysregulation of neuronal SOCE and glutamate receptor activity are hallmarks of acute neurodegenerative diseases (e.g., traumatic brain injury and
cerebral ischemia
) and chronic neurodegenerative diseases (e.g., Alzheimer's disease and Huntington's disease). Emerging evidence indicates a role for STIM proteins and glutamate receptors in neuronal physiology and pathology, making them potential therapeutic targets.
...
PMID:STIM Proteins and Glutamate Receptors in Neurons: Role in Neuronal Physiology and Neurodegenerative Diseases. 3107 35
