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

The incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) among the Chamorros in Guam is remarkably high. The patients with ALS have clinical and pathological characteristics similar to those in other parts of the world. The PDC patients display parkinsonism and progressive dementia and show a characteristic neuronal loss in certain parts of the central nervous system such as the hippocampus and substantia nigra. The Guamanian patients with ALS and PDC commonly have widespread Alzheimer's neurofibrillary changes, but without the associated senile plaques. We have applied immunohistochemical procedures to examine the expression of marker substances in Guamanian ALS and PDC. The markers studied include tau protein, ubiquitin, beta proteins, synaptophysin, calcineurin, Met-enkephalin, substance P and tyrosine hydroxylase. The results were compared with the findings in patients with Alzheimer's disease, Parkinson's disease, sporadic ALS and familial ALS.
 ...
PMID:Amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam: immunohistochemical studies. 158 17

A comparative topographical immunohistochemical analysis was performed on the basal ganglia (including the substantia nigra) in Guamanian parkinsonism-dementia complex, idiopathic Parkinson's disease (PD), and Alzheimer's disease (AD). The striatal projection neurons and their efferent fibers were examined by using antibodies to calcineurin, methionine-enkephalin, and substance P. Tyrosine hydroxylase served as a marker for nigrostriatal dopaminergic neurons. The basal ganglia of patients with parkinsonism-dementia complex reacted strongly with all of the antibodies and the reaction products exhibited a normal distribution pattern. These findings suggest that the striatal output system is well preserved in patients with this disease. Similar results were obtained in patients with AD or PD. However, as compared to the patients with AD or PD, patients with parkinsonism-dementia complex showed severe reduction (greater than 90%) in the number of dopaminergic neurons in both the lateral and the medial portions of the substantia nigra. In view of the functional cortico-subcortical loops, these findings could explain the parkinsonian features and in part the cognitive impairment that occur in parkinsonism-dementia complex on Guam.
 ...
PMID:Immunohistochemical study of the striatal efferents and nigral dopaminergic neurons in parkinsonism-dementia complex on Guam in comparison with those in Parkinson's and Alzheimer's diseases. 169 18

Substance P-like immunoreactivity, choline acetyltransferase (ChAT) activity and muscarinic cholinergic receptors were measured in brains from 9 individuals with senile dementia of the Alzheimer type (AD), 4 individuals with multi-infarct dementia (MID), 6 individuals with mixed type of dementia (AD/MID) and 9 controls. The ChAT activity was markedly reduced (50-60%) in the hippocampus of all demented brains. The number of muscarinic cholinergic receptors was reduced only in the MID and AD/MID brains. No significant difference in substance P-like immunoreactivity was measured in 4 regions of AD brains in comparison to controls. In the combined MID plus AD/MID groups a significant reduction in substance P-like immunoreactivity (-35%) was measured in the hippocampus while no change was found in the frontal cortex, amygdala and caudate nucleus. The findings support the assumption of differences in selectivity of damage between AD and AD/MID, MID.
 ...
PMID:Substance P-like immunoreactivity, choline acetyltransferase activity and cholinergic muscarinic receptors in Alzheimer's disease and multi-infarct dementia. 169 12

Alzheimer's disease (AD) is one of more than 60 disorders that may produce dementia. It is characterized clinically by memory deficits and by the presence of aphaso-apracto-agnosic disorders. In the general population, AD has an incidence of 0.3 to 1% and is very common in the elderly (more than 50% of dementia cases). The pattern of pathological changes in the brain in AD is relatively specific. Neuritic plaques, neurofibrillary tangles and cell loss, occur primarily in the cerebral neocortex and hippocampus. On the other hand, neurochemical deficiencies related to the illness have now been identified. The vulnerability of the cholinergic system of the basal nucleus of Meynert was first documented. Following the discovery of the cholinergic reduction in AD and among a dozen of neurotransmitter systems involved in AD, somatostatin, substance P, neuropeptide Y, corticotropin releasing factor and amino acid glutamate were investigated and are the most affected in AD. Results of previous publications and our own investigations are presented here.
 ...
PMID:[Neuromodulators and Alzheimer's disease]. 246

Substance P is found in both the basal ganglia and cerebral cortex in mammalian brain. In the present study postmortem concentrations of substance P-like immunoreactivity (SP-LI) were measured in the globus pallidus, substantia nigra and 22 cortical regions in a group of demented patients with neuropathological features of both Parkinson's disease (PD) and Alzheimer's disease (AD), and from neurologically normal controls. There were no significant changes in the globus pallidus but concentrations were significantly reduced by 44% in the substantia nigra compacta in the PD patients. In cerebral cortex small (20-30%) significant reductions of SP-LI were found in the PD patients in 7 of 22 cortical regions examined. These results are similar to changes found in AD alone and provide further evidence that the dementia of PD is frequently related to the coincidence of PD and AD.
 ...
PMID:Substance P-like immunoreactivity in brains with pathological features of Parkinson's and Alzheimer's diseases. 247 78

In Parkinson's disease the progressive loss of nigrostriatal dopamine neurons leads to striatal dopamine deficiency and correlates with the severity of parkinsonian disability. The findings concerning dopamine receptors both in vitro and in vivo are not consistent, possibly reflecting differences in patient populations, but the presynaptic defect in dopaminergic neurotransmission is greater than that seen in postsynaptic receptor binding studies. The cholinergic neurons in the extrapyramidal nuclei are relatively well preserved, but subcortico-cortical and -hippocampal cholinergic neurons degenerate in relation to the degree of dementia. The decreased GABA receptor binding in the parkinsonian substantia nigra possibly reflects the loss of nigral dopamine neurons, since nigral GABA receptors are located on these neurons. Of the various neuropeptides, the concentration of met- and leu-enkephalin seems to be reduced in the striatum. In the substantia nigra the concentration of substance P decreases, together with the met-enkephalin and cholecystokinin levels. The concentration of somatostatin decreases in the frontal cortex and hippocampus of demented patients. With the exception of the association between cortical somatostatin deficiency and intellectual deterioration, the role of the neuropeptides in the pathophysiology and clinical features of Parkinson's disease are not yet fully understood.
 ...
PMID:Chemical neurotransmission in the parkinsonian brain. 282 31

Alzheimer's disease (AD) and senile dementia (SD) are often classified together, but there are genetic, biochemical, neuropathological and clinical arguments for separating them. The well-known Alzheimer lesions in the brains of patients with AD and SD are described, as is the loss of neurons in the locus coeruleus. White matter changes in brains from patients with dementia are discussed and related to AD and SD. Biochemical changes in brains of patients with AD and SD include reduced activity of acetylcholinesterase (AChE) and choline-acetyltransferase (CAT), indicating reduced activity in the acetylcholinergic system. There is also, however, reduced activity in the dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) system. The active amines are decreased while the end metabolites are decreased to a lesser extent or normal. The levels of the active amines are thought to reflect the number of neurons, while the levels of end metabolites reflect the rate of turnover in the system. 3-Methoxy-4-hydroxyphenylglycol (MHPG) is increased to levels above normal, which may indicate an increased rate of turnover in the NA system. Monoamine oxidase B (MAO-B), which is increased in advanced age, is further increased in patients with AD and SD. It is assumed that this enzyme is localized in extraneuronal tissue, and therefore the increase may reflect a gliosis. In brains from patients with AD and SD neuropeptides are also studied. Only somatostatin and substance P, however, seem to be reduced, indicating selective damage to the neuropeptides. The biochemical changes can be given pathogenetic importance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alzheimer's disease and senile dementia: biochemical characteristics and aspects of treatment. 286 36

Parkinson's disease is characterized by a deficiency of dopamine in the nigrostriatal system. However, changes in dopamine neurons were found also outside the extrapyramidal system, showing that there is a more general brain defect than just the loss of substantia nigra dopamine neurons. With regard to the behavior of striatal D-2 receptors it was possible to divide parkinsonian patients into two subgroups, because either a decrease or an increase in the number of D-2 receptors was found. Clinically, the patients with a decreased number of striatal D-2 receptors were more disabled and had lost the beneficial response to levodopa. D-3 receptor binding sites were decreased in the parkinsonian striatum. Changes in the cholinergic-muscarinic receptors in the striatum seem to be related to changes in D-2 receptors, and muscarinic receptor supersensitivity was found in cortical areas. GABA receptor binding was decreased in the substantia nigra. In the parkinsonian brain there seems to be supersensitivity of a population of enkephalin receptors (delta) in the striatum and in the limbic system and also a loss of others (mu) in the striatum. Furthermore, the Met-enkephalin content was decreased in the parkinsonian substantia nigra. A decreased concentration of substance P was found in the substantia nigra of all parkinsonian patients and in the putamen of those patients who had not received levodopa treatment. The somatostatin level was decreased in the frontal cortex in relation to dementia. There are thus multiple neuronal disturbances in the parkinsonian brain, although those of the nigrostriatal dopamine neurons seem to be the greatest and are more closely related to parkinsonian clinical features and to treatment responses.
 ...
PMID:Brain neurotransmitters and neuropeptides in Parkinson's disease. 609 88

The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi-infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and paleocortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.
 ...
PMID:Senile dementia of the Alzheimer type. 613 75

Neurochemical and histochemical techniques for characterization of neurotransmitters and their receptors in normal and pathological human brain have modified our understanding of Alzheimer's disease. From a hopeless clinico-pathological entity, it has become one of the models of possible physiopathological relations between neurotransmitter anomalies and dementia processes. Three types of neuromediator (or neuro-modulator): cholinergic, aminergic and peptidergic, appear to be affected to different degrees in 5 electively involved anatomical systems: cholinergic innominocorticoamygdalian and septohippocampic systems, noradrenergic ceruleocortical system, serotoninergic pontocortical system and cortical somatostatin and substance P systems. Critical analysis of neurochemical data shows that the biochemical nosology of Alzheimer's disease is confronted by the difficulty of constituting homogeneous series of both normal and pathological cases. Difficulties are increased when an attempt is made to establish correlations between neurotransmitter deficits and lesions or the demential process. This is the result of several factors: individual variability, difficulty in selecting valid controls, time elapsed before post-mortem sampling, imperfect understanding of the progressive topographical course of both cortical and subcortical lesions, which only now are being studied systematically and in a quantifiable manner, and finally the frequent absence of distinction between early and late forms of the disease. Truly senile forms should probably be distinguished, some authors believing them to be a particular type of aging process, from the presenile forms with more extensive biochemical changes. The constant presence of cholinergic symptoms show these to be fundamental features of the dementia but lesions of noradrenergic and serotoninergic systems also probably play an important role, and this triad is found in other dementia processes: trisomy 21, Parkinson's disease with dementia. Numerous questions concerning the neurotransmitter disorders in Alzheimer's disease remain unanswered: to what extent are the lesions due to neurone destruction? What occurs to the receptors? What factors condition severity of the disease? May the latter be directly correlated with the severity of the global dementia process or rather with the constitutive elements of the syndrome such as memory or attention disorders? What are the consequences of the peptidergic lesions? What is the sequential relation between lesions of corticopetal and intracortical afferent systems and what are their respective physiopathological significance?(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Neurotransmitter anomalies in Alzheimer's disease]. 615 May 45


1 2 3 Next >>