Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The function of the nervous system relies upon synaptic transmission, a process in which a neurotransmitter released from pre-synaptic terminals of one neuron (in response to membrane depolarization and calcium influx) activates post-synaptic receptors on dendrites of another neuron. Synapses are subjected to repeated bouts of oxidative and metabolic stress as the result of changing ion gradients and ATP usage. Mitochondria play central roles in meeting the demands of synapses for ATP and in regulating calcium homeostasis, and mitochondrial dysfunction can cause dysfunction and degeneration of synapses, and can trigger cell death. We have identified two types of mitochondrial proteins that serve the function of protecting synapses and neurons against dysfunction and death. Mitochondrial ATP-sensitive potassium (MitoKATP) channels modulate inner membrane potential and oxyradical production; mitochondrial potassium fluxes can affect cytochrome c release and caspase activation and may determine whether neurons live or die in experimental models of stroke and Alzheimer's disease. Uncoupling proteins (UCPs) are a family of mitochondrial membrane proteins that uncouple electron transport from ATP production by transporting protons across the inner membrane. Neurons express at least three UCPs including the widely expressed UCP-2 and the neuron-specific UCP-4 and UCP-5 (BMCP-1). We have found that UCP-4 protects neurons against apoptosis by a mechanism involving suppression of oxyradical production and stabilization of cellular calcium homeostasis. The expression of UCP-4 is itself regulated by changes in energy metabolism. In addition to their roles in neuronal cell survival and death, MitoKATP channels and UCPs may play roles in regulating neuronal differentiation during development and synaptic plasticity in the adult.
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PMID:Mitochondrial potassium channels and uncoupling proteins in synaptic plasticity and neuronal cell death. 1272 89

Uncoupling proteins (UCPs) are reported to regulate mitochondrial respiration and energy metabolism during hibernation. Recently, it has been reported that UCP2 and UCP5 might reduce free radical stress in the ischemic condition in in vitro models, suggesting both as potential neuroprotective agents. We therefore investigated the levels of UCP2 and UCP5 expression in the lesion of human brain infarction. Brain slice sections were prepared from pathological samples collected at our hospital. Embolic stroke brains sectioned because of the stroke (n = 5) and multiple brain infarction with several stroke episodes (n = 4) were selected for this study. We observed the amount of UCP2 and UCP5 expression in both lesioned and intact areas, and compared them between embolic stroke and multiple infarction cases. The results showed that the expression of UCP2 and UCP5 was significantly elevated in the ischemic lesions compared to the intact area. UCP5 expression in the lesions was higher in multiple infarction cases than in embolic stroke cases. In conclusion, brains may respond to neuroprotection through the increased expression of UCP2 and UCP5 under ischemic conditions. Moreover, UCP5 may respond to repetitive ischemic stresses or have a long-term effect.
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PMID:Amplified expression of uncoupling proteins in human brain ischemic lesions. 1801 77