Abstract：
:Certain serine proteases from the circulation (e.g., coagulation factors), inflammatory cells (e.g., mast-cell tryptase, neutrophil proteinase 3), and from many other cell types (e.g., trypsins) can specifically signal to cells by cleaving protease-activated receptors (PARs), a family of four G protein-coupled receptors. Proteases cleave PARs at specific sites within the extracellular amino-terminus to expose amino-terminal tethered ligand domains that bind to and activate the cleaved receptors. The proteases that activate PARs are often generated and released during injury and inflammation, and activated PARs orchestrate tissue responses to injury, including hemostasis, inflammation, pain, and repair. This review concerns protease and PAR signaling in the nervous system. Neurons of the central and peripheral nervous systems express all four PARs. Proteases that may derive from the circulation, inflammatory cells, or neural tissues can cleave PARs on neurons and thereby activate diverse signaling pathways that control survival, morphology, release of neurotransmitters, and activity of ion channels. In this manner proteases and PARs regulate neurodegeneration, neurogenic inflammation, and pain transmission. Thus, PARs may participate in disease states and PAR antagonists or agonists may be useful therapies for certain disorders.
journal_name
Neuromolecular Medjournal_title
Neuromolecular medicineauthors
Saito T,Bunnett NWdoi
10.1385/NMM:7:1-2:079keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
79-99issue
1-2eissn
1535-1084issn
1559-1174pii
NMM:7:1-2:079journal_volume
7pub_type
杂志文章,评审abstract：:We have previously reported that mild traumatic brain injury (mTBI) induced cognitive deficits as well as apoptotic changes in the brains of mice. Apoptosis may be caused by severe, prolonged accumulation of misfolded proteins, and protein aggregation in the endoplasmic reticulum (ER stress). In an additional study, w...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-015-8340-3
更新日期：2015-03-01 00:00:00
abstract：:Physical exercise has long been recognized as highly beneficial for brain and body health. The molecular mechanisms responsible for translation of exercise stimuli in the brain have claimed attention due to mounting evidence for the neuroprotective actions of the exercise and its positive effects in preventing both ag...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1007/s12017-008-8026-1
更新日期：2008-01-01 00:00:00
abstract：:Attention deficit hyperactivity disorder (ADHD) is a behavioral diagnosis based on the presence of developmentally inappropriate levels of impulsivity, overactivity, and inattentiveness. It is a familial condition with a complex pattern of inheritance. Variation of several genes involved in the regulation of dopamine,...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1385/NMM:8:4:461
更新日期：2006-01-01 00:00:00
abstract：:The high-metabolic demand of neurons and their reliance on glucose as an energy source places them at risk for dysfunction and death under conditions of metabolic and oxidative stress. Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins implicated in the regulation of mitochondrial membrane potential ...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1385/NMM:8:3:389
更新日期：2006-01-01 00:00:00
abstract：:There is increasing evidence implicating apoptosis-mediated cell death in the pathogenesis of neurodegenerative diseases. One important event in the apoptotic cascade is the release of cytochrome c by mitochondria into the cytoplasm, activating caspase-9, leading to the subsequent activation of downstream executioner ...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1385/NMM:1:3:183
更新日期：2002-01-01 00:00:00
abstract：:Clathrin assembly proteins AP180 and CALM regulate the assembly of clathrin-coated vesicles (CCVs), which mediate diverse intracellular trafficking processes, including synaptic vesicle (SV) recycling at the synapse. Although studies using several invertebrate model systems have indicated a role for AP180 in SV recycl...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-012-8194-x
更新日期：2013-03-01 00:00:00
abstract：:In addition to myelin loss and oligodendrocyte injury, axonal damage is a major cause of irreversible neurological disability in multiple sclerosis (MS). A series of studies have demonstrated that Rho kinase (ROCK) is involved in synaptic plasticity of neurons. Here, we found that ROCK activity in MS serum was elevate...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-015-8374-6
更新日期：2015-12-01 00:00:00
abstract：:More than 30 genetic causes have been identified for the inherited neuropathies collectively referred to as Charcot-Marie-Tooth (CMT) disease. Previous therapies for CMT were limited to traditional approaches such as rehabilitation medicine, ambulation aids, and pain management. Identification of the genes causing CMT...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1385/nmm:8:1-2:255
更新日期：2006-01-01 00:00:00
abstract：:The X-linked form of Charcot-Marie-Tooth disease (CMT1X) is the second most common molecularly designated form of hereditary motor and sensory neuropathy. The clinical phenotype is characterized by progressive distal muscle atrophy and weakness, areflexia, and variable sensory abnormalities. Affected males have modera...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1385/nmm:8:1-2:107
更新日期：2006-01-01 00:00:00
abstract：:Stroke is the second foremost cause of mortality worldwide and a major cause of long-term disability. Due to changes in lifestyle and an aging population, the incidence of stroke continues to increase and stroke mortality predicted to exceed 12 % by the year 2030. However, the development of pharmacological treatments...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1007/s12017-016-8403-0
更新日期：2016-09-01 00:00:00
abstract：:The wide use of serotonin reuptake inhibitors and serotonin receptor agonists in anxiety disorders has suggested a key role for the modulatory neurotransmitter in anxiety. However, serotonin's specific role is still uncertain. This article reviews the literature concerning how and where serotonergic agents modulate an...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1385/NMM:5:1:027
更新日期：2004-01-01 00:00:00
abstract：:Hereditary sensory and autonomic neuropathy 1 (HSAN1) is an autosomal dominant disorder that can be caused by variants in SPTLC1 or SPTLC2, encoding subunits of serine palmitoyl-CoA transferase. Disease variants alter the enzyme's substrate specificity and lead to accumulation of neurotoxic 1-deoxysphingolipids. We de...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-015-8379-1
更新日期：2016-03-01 00:00:00
abstract：:Origins of onset and progression of motor neurodegeneration in amyotrophic lateral sclerosis (ALS) are not clearly known, but may include impairment of mitochondrial bioenergetics. We used quantitative PCR approaches to analyze the mitochondrial oxidative phosphorylation (OXPHOS) transcriptomes of spinal cord tissue a...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-014-8321-y
更新日期：2014-12-01 00:00:00
abstract：:Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and epilepsy. The disease is caused by a pentanucleotide ATTCT expansion in intron 9 of the ATXN10 gene on chromosome 22q13.3. SCA10 has shown a geographical distribution throughout...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-017-8464-8
更新日期：2017-12-01 00:00:00
abstract：:Parkinson' disease (PD) is characterized by motor symptoms including bradykinesia, resting tremor, postural instability, and rigidity and non-motor symptoms such as cognitive impairment, sleep disorder, and depression. Neuroinflammation has been recently implicated in pathophysiology of both motor and non-motor sympto...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-018-8499-5
更新日期：2018-09-01 00:00:00
abstract：:Substantial evidence indicates bioenergetic dysfunction and mitochondrial impairment contribute either directly and/or indirectly to the pathogenesis of numerous neurodegenerative disorders. Treatment paradigms aimed at ameliorating this cellular energy deficit and/or improving mitochondrial function in these neurodeg...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1007/s12017-008-8053-y
更新日期：2008-01-01 00:00:00
abstract：:T-cells directed to self-antigens ("autoimmune" T-cells) have traditionally been perceived as tending to attack the body's own tissues, and likely to exert their destructive effects unless they undergo deletion in the thymus during ontogeny. Naturally occurring CD4+CD25+ regulatory T-cells were viewed as thymus-derive...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1385/NMM:7:3:197
更新日期：2005-01-01 00:00:00
abstract：:Autism spectrum disorder (ASD) is a heterogeneously childhood neurodevelopmental disorder, believed to be under development of various genetic and environmental factors. Autophagy and related pathways have also been implicated in the etiology of ASD. We aimed to investigate autophagic markers by generating the transge...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-019-08579-x
更新日期：2020-06-01 00:00:00
abstract：:The metabolic syndrome is characterized by the clustering of various common metabolic abnormalities in an individual and it is associated with increased risk for the development of type 2 diabetes and cardiovascular diseases. Its prevalence in the general population is approximately 25%. Central fat accumulation and i...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1007/s12017-008-8022-5
更新日期：2008-01-01 00:00:00
abstract：:Hemorrhagic transformation (HT) of cerebral infarction is a common and serious occurrence following acute ischemic stroke. The expression of survivin, a member of the inhibitor of apoptosis protein family, has been shown to increase after cerebral ischemia. This protein has been mainly located at the microvasculature ...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-014-8333-7
更新日期：2014-12-01 00:00:00
abstract：:The present study demonstrates the efficacies of synthetic 1,8-cineole and an 1,8-cineole-rich supercritical carbon dioxide (SC-CO2) extract of small cardamom seeds in preventing oligomerization of amyloid beta peptide (Aβ42) and inhibiting iron-dependent oxyradical production in vitro. The oligomerization of Aβ42 was...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-019-08574-2
更新日期：2020-03-01 00:00:00
abstract：:Neurons and especially their synapses often project long thin processes that can invaginate neighboring neuronal or glial cells. These "invaginating projections" can occur in almost any combination of postsynaptic, presynaptic, and glial processes. Invaginating projections provide a precise mechanism for one neuron to...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1007/s12017-015-8358-6
更新日期：2015-09-01 00:00:00
abstract：:The frequent co-occurrence of autism spectrum disorders (ASD) and epilepsy, or paroxysmal EEG abnormalities, defines a condition termed autism-epilepsy phenotype (AEP). This condition results, in some cases , from dysfunctions of glial inwardly rectifying potassium channels (Kir), which are mainly expressed in astrocy...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-015-8378-2
更新日期：2016-03-01 00:00:00
abstract：:The cerebral ischemia is one of the most common diseases in the central nervous system that causes progressive disability or even death. In this connection, the inflammatory response mediated by the activated microglia is believed to play a central role in this pathogenesis. In the event of brain injury, activated mic...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1007/s12017-016-8394-x
更新日期：2016-09-01 00:00:00
abstract：:Danshensu (DSS) and tetramethylpyrazine (TMP) are active ingredients of Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort that are widely used in oriental medicine. Structural combination of compounds with known biological activity may lead to the formation of a molecule with multiple properties or new function ...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-016-8399-5
更新日期：2016-12-01 00:00:00
abstract：:Cardiovascular diseases including hypertension, myocardial infarction, stroke, and heart failure continue to account for the majority of deaths in the developed world. Whilst the incidence of these clinical disorders does increase with age, outcomes in affected patients tend to be disproportionately adverse with advan...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1007/s12017-008-8034-1
更新日期：2008-01-01 00:00:00
abstract：BACKGROUND:Scutellarin, an herbal compound, can effectively suppress the inflammatory response in activated microglia/brain macrophage(AM/BM) in experimentally induced cerebral ischemia; however, the underlying mechanism for this has not been fully clarified. We sought to elucidate if scutellarin would exert its anti-i...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-019-08582-2
更新日期：2020-06-01 00:00:00
abstract：:Accumulating studies have suggested the important role of microRNA (miRNA) in ischemic cerebral infarction. However, little is known of the modifying effect of miR-5787, a newly found miRNA, in ischemic cerebral infarction. We aim to elucidate the effect and underlying molecular mechanism of miR-5787 in the pathogenes...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-020-08628-w
更新日期：2020-11-09 00:00:00
abstract：:Rett syndrome is a severe neurodevelopmental disorder, almost exclusively affecting females and characterized by a wide spectrum of clinical manifestations. Both the classic and atypical forms of Rett syndrome are primarily due to mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Mutations in the X-linked cy...
journal_title：Neuromolecular medicine
pub_type： 杂志文章
doi：10.1007/s12017-012-8212-z
更新日期：2013-03-01 00:00:00
abstract：:Sphingosine 1-phosphates (S1Ps) are bioactive lipids that mediate a diverse range of effects through the activation of cognate receptors, S1P1-S1P5. Scrutiny of S1P-regulated pathways over the past three decades has identified important and occasionally counteracting functions in the brain and cerebrovascular system. ...
journal_title：Neuromolecular medicine
pub_type： 杂志文章,评审
doi：10.1007/s12017-020-08632-0
更新日期：2020-11-12 00:00:00
