Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report the sixth case of Menkes' kinky hair disease. This boy has been observed for as long as 16 months, and he his still alive at the time of publication. This genetic, X linked disorder of copper metabolism is always fatal in childhood. Diagnosis is evoked when is noted the conjunction of progressive cerebral degeneration, seizures, with pili torti and monilethrix. It can be asserted with the very low copper and cerulo-plasmin blood levels. Recognition of the disease in utero might be possible. New findings in skin' electron microscopy and hair' scanning electron microscopy are reported here. And two RX scanner of the brain have been performed.
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PMID:[Menkes' disease (new skin and hair ultrastructural abnormalities) (author's transl)]. 70 42

Neuronal degeneration in the hippocampus, a region of the brain important for acquisition of memory in humans, occurs in various pathological conditions, including Alzheimer's disease, brain ischaemia and epilepsy. When neuronal activity is stimulated in the adult rat and mouse hippocampus, tissue plasminogen activator (tPA), a serine protease that converts inactive plasminogen to the active protease plasmin, is transcriptionally induced. The activity of tPA in neural tissue is correlated with neurite outgrowth, regeneration and migration, suggesting that it might be involved in neuronal plasticity. Here we show that tPA is produced primarily by microglia in the hippocampus. Using excitotoxins to induce neuronal cell loss, we demonstrate that tPA-deficient mice are resistant to neuronal degeneration. These mice are also less susceptible to pharmacologically induced seizures than wild-type mice. These findings identify a role for tPA in neuronal degeneration and seizure.
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PMID:Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. 756 88

Neuronal migration is a critical phase of brain development, where defects can lead to severe ataxia, mental retardation, and seizures. In the developing cerebellum, granule neurons turn on the gene for tissue plasminogen activator (tPA) as they begin their migration into the cerebellar molecular layer. Granule neurons both secrete tPA, an extracellular serine protease that converts the proenzyme plasminogen into the active protease plasmin, and bind tPA to their cell surface. In the nervous system, tPA activity is correlated with neurite outgrowth, neuronal migration, learning, and excitotoxic death. Here we show that compared with their normal counterparts, mice lacking the tPA gene (tPA(-/-)) have greater than 2-fold more migrating granule neurons in the cerebellar molecular layer during the most active phase of granule cell migration. A real-time analysis of granule cell migration in cerebellar slices of tPA(-/-) mice shows that granule neurons are migrating 51% as fast as granule neurons in slices from wild-type mice. These findings establish a direct role for tPA in facilitating neuronal migration, and they raise the possibility that late arriving neurons may have altered synaptic interactions.
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PMID:Neuronal migration is retarded in mice lacking the tissue plasminogen activator gene. 1057 Feb 8

Short seizure episodes are associated with remodeling of neuronal connections. One region where such reorganization occurs is the hippocampus, and in particular, the mossy fiber pathway. Using genetic and pharmacological approaches, we show here a critical role in vivo for tissue plasminogen activator (tPA), an extracellular protease that converts plasminogen to plasmin, to induce mossy fiber sprouting. We identify DSD-1-PG/phosphacan, an extracellular matrix component associated with neurite reorganization, as a physiological target of plasmin. Mice lacking tPA displayed decreased mossy fiber outgrowth and an aberrant band at the border of the supragranular region of the dentate gyrus that coincides with the deposition of unprocessed DSD-1-PG/phosphacan and excessive Timm-positive, mossy fiber termini. Plasminogen-deficient mice also exhibit the laminar band and DSD- 1-PG/phosphacan deposition, but mossy fiber outgrowth through the supragranular region is normal. These results demonstrate that tPA functions acutely, both through and independently of plasmin, to mediate mossy fiber reorganization.
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PMID:The tissue plasminogen activator (tPA)/plasmin extracellular proteolytic system regulates seizure-induced hippocampal mossy fiber outgrowth through a proteoglycan substrate. 1072 41

The protective blood-brain barrier normally allows diffusion of small molecules such as oxygen and carbon dioxide, and transport of essential nutrients, but excludes large proteins and other blood constituents from the interstitial space of the CNS. However, head trauma, stroke, status epilepticus and other pathological conditions can all compromise the integrity of this barrier, and allow blood proteins as large as albumin to gain access to the extracellular spaces that surround neurons and glia. Given their possible entry into brain tissue during cerebrovascular insult, the effects of blood-derived proteases such as thrombin, tissue plasminogen activator and plasmin in the CNS have come under increasing scrutiny. Evidence now supports a role for serine proteases in the sequence of events that can lead to glial scarring, edema, seizure and neuronal death.
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PMID:Serine proteases and brain damage - is there a link? 1126 39

Tissue plasminogen activator (tPA) is a serine protease that converts plasminogen to plasmin. It plays an important role in the nervous system, including the processes of neuronal migration, neurite outgrowth, and neuronal plasticity. tPA has also been suggested to have a role in several neuropathological conditions, such as cerebral ischemia, seizures, and demyelinating diseases. To investigate the role of tPA in spinal cord injury, wild-type mice and mice with homozygous tPA deficiency (tPA(-/-) mice) were subjected to spinal cord contusion and the differences of hindlimb function, electrophysiological changes, and histopathological changes were assessed for 6 weeks. Functional recovery was greater in tPA(-/-) mice than in wild-type mice throughout the observation period. The time course of myoelectric motor-evoked potentials supported the hindlimb functional findings. Histological examination showed that injured areas were smaller in tPA(-/-) mice than wild-type mice on Luxol fast blue staining or myelin basic protein and neurofilament protein immunostaining at 6 weeks after contusion. Electron microscopy showed that the white matter was better preserved in tPA(-/-) mice than in wild-type mice. The expression of tPA protein was widespread on the first day after contusion and this expression was detected for at least a week. Activation of microglia/macrophages and apoptotic cell death were significantly reduced in tPA(-/-) mice after contusion. This study shows that neural damage is decreased in tPA(-/-) mice after spinal cord injury. Suppression of tPA production may help to decrease secondary injury after spinal cord contusion.
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PMID:Decreased neural damage after spinal cord injury in tPA-deficient mice. 1261 87

Tissue-type plasmingen activator (tPA) is a highly specific serine proteinase that activates the zymogen plasminogen to the broad-specificity proteinase plasmin. tPA is found in the blood, where its primary function is as a thrombolytic enzyme, as well as in the central nervous system (CNS), where it promotes events associated with synaptic plasticity and cell death in a number of settings, such as cerebral ischemia and seizures. Neuroserpin is a fully inhibitory serine proteinase inhibitor (serpin) that reacts preferentially with tPA, and is located in regions of the brain where either tPA message or tPA protein are also found, suggesting that neuroserpin is the selective inhibitor of tPA in the CNS. There is a growing body of evidence demonstrating the participation of tPA in a number of physiologic and pathologic events in the CNS, and the role of neuroserpin as the natural regulator of tPA's activity in these processes.
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PMID:Tissue-type plasminogen activator and neuroserpin: a well-balanced act in the nervous system? 1526 88

Tissue-type plasminogen activator (tPA) is a highly specific serine proteinase that activates the zymogen plasminogen to the broad-specificity proteinase plasmin. Tissue-type plasminogen activator is found not only in the blood, where its primary function is as a thrombolytic enzyme, but also in the central nervous system (CNS), where it promotes events associated with synaptic plasticity and acts as a regulator of the permeability of the neurovascular unit. Tissue-type plasminogen activator has also been associated with pathological events in the CNS such as cerebral ischemia and seizures. Neuroserpin is an inhibitory serpin that reacts preferentially with tPA and is located in regions of the brain where either tPA message or tPA protein are also found, indicating that neuroserpin is the selective inhibitor of tPA in the CNS. There is a growing body of evidence demonstrating the participation of tPA in a number of physiological and pathological events in the CNS, as well as the role of neuroserpin as the natural regulator of tPA's activity in these processes. This review will focus on nonhemostatic roles of tPA in the CNS with emphasis on its newly described function as a regulator of permeability of the neurovascular unit and on the regulatory role of neuroserpin in these events.
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PMID:New functions for an old enzyme: nonhemostatic roles for tissue-type plasminogen activator in the central nervous system. 1556 35

Neuroserpin is a member of the serpin family of serine protease inhibitors. Tissue distribution analysis reveals a predominantly neuronal expression during the late stages of neurogenesis and, in the adult brain, in areas where synaptic changes are associated with learning and memory (synaptic plasticity). In vitro studies revealed complex formation between neuroserpin and different serine proteases, i.e. tPA, uPA, and plasmin. The neuroserpin-target complex has so far not been characterized in vivo. However, some investigations help to understand the functional role of this serpin. Neuroserpin was shown to be involved in the regulation of the morphology of neuroendocrine cells in culture, possibly by modulating the degradation of the extracellular matrix by proteolytic enzymes such as tPA. Moreover, a role of neuroserpin in mood regulation has been deduced from the over- and underexpression of neuroserpin in genetically modified mice, which showed increased anxiety and novelty-induced hypo-locomotion. In pathological conditions of the central nervous system (i.e. stroke and seizures), neuroserpin plays a neuroprotective role, probably by blocking the deleterious effects of tPA. A familial form of a neurodegenerative disease, termed familial encephalopathy with neuroserpin inclusion bodies, is caused by point mutations in the neuroserpin gene. This condition is characterized by the intracellular polymerization and accumulation of mutated neuroserpin, leading to neuronal death and dementia.
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PMID:Neuroserpin. 1614 12

Protein tyrosine phosphatase receptor type Z (Ptprz, also known as PTPzeta or RPTPbeta) is preferentially expressed in the CNS as a major chondroitin sulfate proteoglycan (CSPG). Ptprz interacts with the PSD95 family through its intracellular carboxyl-terminal PDZ-binding motif in the postsynaptic density. Ptprz-deficient adult mice display impairments in spatial and contextual learning. Here, we identified the proteolytic processing of Ptprz by plasmin in the mouse brain, which is markedly enhanced after kainic acid (KA)-induced seizures. We mapped plasmin cleavage sites in the extracellular region of Ptprz by cell-based assays and in vitro digestion experiments with recombinant proteins. These findings indicate that Ptprz is a physiological target for activity-dependent proteolytic processing by the tPA/plasmin system, and suggest that the proteolytic cleavage is involved in the functional processes of the synapses during learning and memory.
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PMID:Plasmin-mediated processing of protein tyrosine phosphatase receptor type Z in the mouse brain. 1864 37


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