Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptides are sufficiently stable to allow valid radioimmunoassay of peptide concentrations in post-mortem human nervous tissue and in human cerebrospinal fluid. Studies have now documented abnormalities of peptide concentrations in degenerative diseases of the brain. Somatostatin concentration is reduced in the hippocampus and neocortex of patients dying with Alzheimer's type dementia. In Huntington's disease, there are reduced concentrations of substance P, met-enkephalin and cholecystokinin in the basal ganglia; in contrast the concentrations of somatostatin and TRH are increased. Immunocytochemical and experimental lesion studies are underway in an attempt to localize the peptide-containing cells affected by these disorders; and the potential role of alterations in neuropeptide function in the pathogenesis, clinical manifestations and therapy of these illnesses is of great interest. Although alterations of CSF peptide concentrations have been reported in a variety of human diseases, interpretation of these results requires knowledge of the origin and disposition of CSF peptides. Future research into the pathology of peptidergic systems will depend on the development of specific peptide antagonists to probe dynamic aspects of peptide function and on the application of the tools of molecular biology, such as specific mRNA assays, to human material.
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PMID:Implications of neuropeptides in neurological diseases. 620 11

This report concerns a topographic immunohistochemical analysis of Met-enkephalin (MEnk) and substance P (SP) expression in the striatum from seven patients with parkinsonism-dementia complex on Guam (PDC). The striatum of seven neurologically normal subjects served as controls. MEnk-positive striosomes were readily visualized in both the caudate nucleus and the putamen of the PDC cases. Although the immunoreactivity was less than that of MEnk, SP-positive patches were detected in the PDC striatum. The patches were similar to those seen in the normal controls. These results provide additional evidence that the striatum and its efferent system appear to be preserved in patients with PDC.
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PMID:Striosomal arrangement of met-enkephalin and substance P expression in parkinsonism-dementia complex on Guam. 768 67

Swollen, bulbous-shaped (dystrophic) neurites are a common pathologic feature of Alzheimer's disease (AD) and represent one of the most abundant neuritic abnormalities within the brains of patients with this disease. In the present study, we sought to determine whether the dystrophic neurites which are observed in association with senile plaques are unique to AD or whether they are characteristic of a more generalized process of neuritic and/or neuronal degeneration which can be observed in other neurodegenerative diseases. To accomplish this, we examined post-mortem brain material from patients with AD, Parkinson's disease (PD), Parkinson's disease with associated AD, Parkinson's disease with dementia yet without AD pathology, Huntington's disease (HD), Pick's disease and normal age-matched controls (NC). Using a battery of antibodies to amyloid beta-protein (A beta P), paired-helical filaments (PHF), tyrosine hydroxylase, substance P, neurotensin, and somatostatin we found that immunolabeled dystrophic neurites of the type characteristically observed in AD, were seen only in cases and in brain regions where A beta P deposition was present. More specifically, brain areas known to display severe afferent and/or local degenerative changes such as the caudate and putamen in all three PD groups, the caudate in the HD cases, and the temporal cortex in the HD and Pick's cases were conspicuously free of these swollen neurites unless A beta P deposition was also present.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alzheimer's disease-like dystrophic neurites characteristically associated with senile plaques are not found within other neurodegenerative diseases unless amyloid beta-protein deposition is present. 809 26

Marked specific and selective changes in the levels of some neuropeptides in age-related diseases, such as senile dementia of the Alzheimer (SDAT) or Lewy body (SDLT) types, Parkinson's disease, Huntington's disease and major depressive disorder, versus normal aging have been noted. However, the levels of most neuropeptides are normal. The only 2 peptides consistently altered in SDAT are somatostatin and corticotrophin-releasing hormone both of which are reduced. In Huntington's disease, the level of substance P in the basal ganglia is reduced suggesting a preferential vulnerability of spiny neurones in this disease. In Parkinson's disease, substance P is attenuated in the basal ganglia while somatostatin is reduced in the neocortex. These and other results suggest that substance P deficits are related to movement disorders while somatostatin deficits are related to cognitive impairment. SDLT is a type of dementia with features common to both SDAT and Parkinson's disease, although the changes in neuropeptides suggest that neurochemically the disease is more closely related to SDAT. In major depressive disorder, the level of corticotrophin-releasing hormone is reduced while there is a reciprocal increase in corticotrophin-releasing hormone receptors suggesting that the neurones remain functional. Potential clinical intervention has been limited by problems such as poor penetration of agents into the brain and the short half-lives of neuropeptide agonists and antagonists. However, some currently available agents may act, at least in part, through modulation of neuropeptide pathways, e.g. carbamazepine and alprazolam both modulate the corticotrophin-releasing hormone system in animals, and both have clinically proven antidepressant activity.
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PMID:Alterations in neuropeptides in aging and disease. Pathophysiology and potential for clinical intervention. 824 6

We have previously reported increased somatostatin levels in the cerebral cortex of rats housed in impoverished environment and subsequently subjected to a behavioural testing procedure, consisting of open-field exposure and spatial learning. The aim of the present study was to evaluate the degree of neurochemical specificity of the activation of somatostatin neurotransmission and to examine whether the altered levels were due to learning stimulation. Adult rats, previously housed individually for 30 days, were exposed to repeated sessions of a spatial learning task (2 days or 14 days) or repeated sessions of free swimming (14 days). The training sessions of the 14 day group consisted in recurrently changed position of the platform in a learning-set paradigm. Our data showed increased somatostatin immunoreactivity, and unchanged substance P immunoreactivity in the posterior part of the cerebral cortex. However, somatostatin levels increased to a similar extent following 14 days of repeated spatial learning sessions as free swimming sessions. We conclude that the activity of the cortical somatostatin system appears to be sensitive to environmentally induced sensorimotor stimulation in general, rather than learning per se. Thus, external stimulation of early clinical dementia patients with preserved sensorimotor receptivity, in an attempt to restore cognitive function, might be associated with altered somatostatin levels.
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PMID:Influence of place learning on somatostatin levels in the rat brain following environmental deprivation. 857 Aug 55

Interleukin-6 (IL-6) is a proinflammatory cytokine whose synthesis is induced by a variety of stimuli including interleukin-1 (IL-1), substance P (SP), and histamine. Because IL-6 has been implicated in the etiopathology of different human diseases including multiple myeloma, rheumatoid arthritis, multiple sclerosis, acquired immunodeficiency syndrome dementia complex, and Alzheimer's disease, its inhibition may be of therapeutic interest. A main demand on an effective inhibitor of IL-6 expression is that it inhibits IL-6 synthesis independently of the inducing stimulus. We therefore used human astrocytoma cells to search for signal transduction cascades and transcription factors whose inhibition suppresses IL-6 synthesis after stimulation with three different inductors, IL-1beta, SP, and histamine. Whereas the antioxidant pyrrolidinedithiocarbamate was only able to inhibit IL-1beta-induced IL-6 expression, inhibition of protein kinase C prevented IL-6 expression induced by all three substances. Promoter deletion analysis revealed that IL-1beta-induced IL-6 expression required the transcription factor nuclear factor-kappaB (NF-kappaB), whereas SP- and histamine-induced IL-6 synthesis was essentially controlled by NF-IL-6. These findings suggest that inhibition of protein kinase C or a combinatory inhibition of NF-IL-6 and NF-kappaB binding are strategies to effectively suppress IL-6 synthesis. They therefore provide the basis for the development of antiinflammatory drugs used to treat disorders in which IL-6 is pathogenically involved.
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PMID:Substance P and histamine induce interleukin-6 expression in human astrocytoma cells by a mechanism involving protein kinase C and nuclear factor-IL-6. 952 75

The concentration of substance P-immunoreactivity (SPIR) in ex vivo lumbar cerebrospinal fluid (CSF) of patients with probable Alzheimer's disease (AD), non-Alzheimer dementias, neurological patients without dementia and control subjects was determined using a sensitive and specific competitive enzyme-immunoassay. There were no significant differences between AD patients and the other groups, but patients with late onset AD (>65 years) showed significantly higher levels of SPIR than patients with early onset (<65 years) and controls. In post mortem ventricular fluid, SPIR levels of all groups were lower compared with the lumbar compartment, but without significant group differences. It is concluded that CSF SPIR may not serve as a diagnostic marker for AD, but possibly could reflect immunological or neuroprotective processes modulated by substance P in late onset AD patients.
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PMID:Ex vivo lumbar and post mortem ventricular cerebrospinal fluid substance P-immunoreactivity in Alzheimer's disease patients. 1116 52

The Rett syndrome (RS) is a peculiar, sporadic, atrophic disorder, almost entirely confined to females. After the first six months of life there is developmental slowing with reduced communication and head growth for about one year. This is followed by a rapid destructive stage with severe dementia and loss of hand skills (with frequent hand wringing), apraxia and ataxia, autistic features and irregular breathing with hyperventilation. Seizures often supervene. Subsequently there is some stabilization in a pseudo-stationary stage during the preschool to school years, associated with more emotional contact but also abnormalities of the autonomic and skeletal systems. After the age of 15-20 years, a late motor deterioration occurs with dystonia and frequent spasticity but seizures become milder. RS has generally been considered an X-linked disorder in which affected females represent a new mutation, with male lethality. Linkage studies suggested a critical region at Xq28. In 1999, mutations in the gene MECP2 encoding X-linked methyl cytosine-binding protein 2 (MeCP2) were found in a proportion of Rett girls. This protein can bind methylated DNA. Analyses are leading to much further investigation of mutants and their effects on genes. Neuropathological and electrophysiological studies of RS are described. Description of neurometabolic factors includes reduced levels of dopamine, serotonin, noradrenaline and choline acetyltransferase (ChAT) in brain, also estimation of nerve growth factors, endorphin, substance P, glutamate and other amino acids and their receptor levels. The results of neuroimaging are surveyed, including volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET).
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PMID:Rett syndrome: review of biological abnormalities. 1125 89

The syndrome of brain atrophy in girls described by Andreas Rett in 1966 [Rett, Wien Klin Wochenschr, 1966;116:723-726] was brought to the attention of the English-speaking world by Hagberg et al. in 1983 [Hagberg et al., Ann Neurol, 1983;14:471-479]. Four clinical stages after the age of 6 months were described in classical cases of Rett syndrome (RS), namely early onset stagnation at 6 months to 1(1/2) years, the rapid destructive stage at 1-3 years, the pseudo-stationary stage from pre-school to school years, and the late motor deterioration stage at 15-30 or more years. The rapid destructive stage causes profound dementia with loss of speech and hand skills, stereotypic movements, ataxia, apraxia, irregular breathing with hyperventilation while awake, and frequently seizures. Most cases are isolated in their families, apart from identical twins. However, linkage studies in rare familial cases suggested a critical region at Xq28. In 1999 American investigators found several mutations in the X-linked gene MECP2 encoding Methyl-CpG-binding protein 2 in a proportion of Rett patients. The protein MeCP2 can bind methylated DNA and when mutated may interfere with transcriptional silencing of other genes and result in abnormal chromatin assembly. Many different mutations of the protein are being studied in humans and in mice. Neuropathological studies have shown decreased brain growth and decreased size of individual neurons, with thinned dendrites in some cortical layers, and abnormalities in substantia nigra, suggestive of deficient synaptogenic development, probably starting before birth. Electrophysiology demonstrates progressively abnormal electroencephalograms (EEG) in the first three stages of the syndrome, with some subsequent improvement and occurrence of pseudoseizures. Neurometabolic factors are discussed in detail, particularly reduced levels of dopamine, serotonin, noradrenaline and choline acetyltransferase (ChAT) in brain, also estimation of nerve growth factors, endorphin, substance P, glutamate and other amino acids and their receptor levels. Autonomic dysfunction is described, particularly reduced vagal and overactive sympathetic activity. Neuro-imaging may be required for further investigation, as shown in the differential diagnosis.
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PMID:Importance of Rett syndrome in child neurology. 1173 40

In this article we show some recent findings that constitute a great progress in the molecular knowledge of synaptic dynamics. To communicate, neurons use a code that includes electrical (action potentials) and chemical signals (neurotransmitters, neuromodulators). At the moment a great variety of molecules are known, whose neurotransmitter function in brain and the peripheral nervous system are out of question. Monoamines like acetylcholine, dopamine, noradrenaline, adrenaline, histamine, serotonin, glutamate, aspartate, glycine, ATP and GABA are good examples. Opioid neuropeptides, vasoactive intestinal peptide (VIP), neurokinines (substance P), somatostatin, neurotensin, neuropeptide Y, cholecystokinine, vasopressin or oxitocin have been related to the control of the stress response, sexual behaviour, food intake, pain, learning and memory, qualities that are also related to nitric oxide (NO). A great part of the molecular structure of the secretory machinery is known to be responsible for fast neurotransmitter release at the synapse, in response to action potentials. Proteins like sinaptobrevin (located in the membrane of the synaptic vesicle), sintaxin and SNAP-25 (both located at the presynaptic plasma membrane) constitute a trimeric complex which is responsible of the vesicular docking at the active sites for exocytosis. From this strategic location, vesicles release their neurotransmitter within few milliseconds, when the action potential invades the nerve terminal and activates the opening of the different subtypes of voltage-dependent Ca2+ channels. The asymmetric geographical distribution of each type of channel, in different neurons, rose the hypothesis that Ca2+ that enters through each subtype of channel is compartmentalised, thus favouring the generation of Ca2+ microdomains, in the cytosol and the nucleus, involved in different cellular functions. This great biochemical synaptic heterogeneity is facilitating the selection of many biological targets to develop drugs with potential therapeutic applications in neuropsychiatric diseases i.e. Alzheimer's, Parkinson, epilepsies, stroke, vascular dementia, depression, schizophrenia, anxiety and so on.
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PMID:[Neurotransmitters, calcium signalling and neuronal communication]. 1515 88


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