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)

The relationship between peptidergic neurites and paired helical filaments (PHF)-positive neurites in Alzheimer's disease (AD) senile plaques (SP) was studied using combined fluorescence and bright field optics. Cryostat sections of AD hippocampi were first stained by thioflavine-S and immunolabeled with antisera raised against different neuropeptides: somatostatin 28(1-12) (som 28(1-12)), somatostatin 14 (som 14), neuropeptide Y (NPY), cholecystokinin (CCK) and substance P (sP). Secondly, using the elution-restaining procedure, sections were immunolabeled with anti-tau/PHF. In immature SP, clusters of abnormal, swollen neurites were found. The dystrophic, strongly peptidic-positive neurites contained less PHF than the poorly positive ones. Cell bodies, exhibiting a peptidic content, could be found within SP without any alteration. These results suggest the following sequence of events: an extracellular poisoning mechanism, perhaps the amyloid substance, first changes the structure of presynaptic endings and causes the formation of ballooning dystrophic neurites filled with their normal peptidic content. Subsequently, intracellular degradation occurs with formation of the PHF. Then the other structures such as dendrites and perikarya are damaged by the same mechanism. Therefore this phenomenon seems to precede any formation of PHF in SP.
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PMID:Dystrophic neuropeptidergic neurites in senile plaques of Alzheimer's disease precede formation of paired helical filaments. 251 78

Aluminum-induced neurofibrillary degeneration in rabbits is known to affect particular populations of neurons. The neurotransmitter alterations which accompany aluminum neurofibrillary degeneration were examined in order to assess how closely they mimic those of Alzheimer's disease. There was a significant reduction in choline acetyltransferase activity in entorhinal cortex and hippocampus as well as significant reductions in cortical concentrations of serotonin and norepinephrine in the aluminum-treated rabbits. Significant reductions in glutamate, aspartate and taurine were found in frontoparietal and posterior parietal cortex. Concentrations of GABA were unchanged in cerebral cortex. Both substance P and cholecystokinin immunoreactivity were significantly reduced in entorhinal cortex but there were no significant changes in somatostatin, neuropeptide Y and vasoactive intestinal polypeptide. The five neuropeptides were unaffected in striatum, thalamus, cerebellum and brainstem. Neurochemical changes were found in the regions with the most neurofibrillary degeneration while regions with little or no neurofibrillary degeneration were unaffected. The reductions in choline acetyltransferase activity, serotinin and noradrenaline suggest that some neuronal populations preferentially affected in Alzheimer's disease are also affected by aluminum-induced neurofibrillary degeneration; however, the cortical somatostatin deficit which is a feature of Alzheimer's disease is not replicated in the aluminum model.
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PMID:Neurochemical characteristics of aluminum-induced neurofibrillary degeneration in rabbits. 256 53

Immunocytochemical studies of the distribution and intensity of Substance P and Met-enkephalin staining in the basal ganglia and substantia nigra were carried out in five cases each of brains from patients with Huntington's disease, Parkinson's disease, Alzheimer's disease, and normal controls. The usefulness of the peroxidase-antiperoxidase method for human autopsy material was confirmed. Substance P and Met-enkephalin fibers were distributed in essentially the same pattern as described in experimental animals and in human brains. In Huntington's disease brains decreased Substance P staining was found in the internal globus pallidus and the substantia nigra, in agreement with radioimmunoassay studies by others. Met-enkephalin staining in the external globus pallidus was of normal intensity, although present within a shrunken area. In Parkinson's and Alzheimer's diseases there was intense immunoreactivity for Substance P in the globus pallidus and substantia nigra, and for Met-enkephalin in the globus pallidus, at variance with reported decreases in Parkinson's disease by radioimmunoassay, but in essential agreement with other immunocytochemical studies. Immunocytochemical methods complement radioimmunoassays of human brain and may help in mapping neuropeptidergic pathways and in pinpointing abnormalities in these pathways in basal ganglia disorders.
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PMID:Immunocytochemical studies of substance P and Met-enkephalin in the basal ganglia and substantia nigra in Huntington's, Parkinson's and Alzheimer's diseases. 257 85

Much interest has recently centred on the properties of peptides that modulate the excitability of nerve cells. Such compounds include the undecapeptide substance P, which is particularly well established as an excitatory neurotransmitter, and we examine here its effects on magnocellular cholinergic neurones taken from the medial and ventral aspects of the globus pallidus of newborn rats and grown in dissociated culture. These neurones have previously been shown to respond to substance P3 and are analogous to the nucleus basalis of Meynert in man, which gives a diffuse projection to the cerebral cortex and whose degeneration is the likely cause of Alzheimer's disease. Substance P depolarizes these cultured neurones by reducing an inwardly rectifying potassium conductances; this conductance has been found in several neuronal types and has similar properties to those of certain other cells. As discussed below, modulation of inward (or anomalous) rectification by substance P implies a self-reinforcing element to the depolarization caused by the peptide.
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PMID:Substance P raises neuronal membrane excitability by reducing inward rectification. 258 70

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)
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PMID:Alzheimer's disease and senile dementia: biochemical characteristics and aspects of treatment. 286 36

In the past twenty years, more than thirty peptides have been discovered to be present in the mammalian central nervous system (CNS). As the neuroanatomical distribution, neurochemical, electrophysiological and pharmacobehavioral effects of this novel group of neuroregulators have been described, it is evident that certain of these peptide-containing neural circuits may be pathologically altered in neuropsychiatric disorders. Although much attention has been focused on the opioid peptides, substantial data strongly support the hypothesis that non-opioid peptides such as somatostatin, neurotensin and substance P are altered in a diverse number of neuropsychiatric disorders including Alzheimer's disease, Huntington's chorea, Parkinson's disease, major depression and schizophrenia.
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PMID:Involvement of non-opioid peptides in the pathogenesis of neurological and psychiatric disorders: evidence from CSF and post-mortem studies. 293 45

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.
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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)
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PMID:[Neurotransmitter anomalies in Alzheimer's disease]. 615 May 45

Activities relating to 3 neurotransmitter and 4 neuropeptide systems have been examined in human temporal lobe (post mortem) for their relationships with age and Alzheimer-type changes (senile plaques and cognitive function). Significant alterations with increasing age (from 61 to 92 years) in a series of non-demented cases included a reduction of the cholinergic enzyme, choline acetyltransferase, and an increase in vasoactive intestinal peptide immunoreactivity. In cases of alzheimer's disease the only neurochemical activity investigated which correlated significantly with cognitive impairment (assessed from a Mental Test Score obtained shortly before death) and with the severity of Alzheimer-type abnormalities (senile plaques density) was choline acetyltransferase. Further analyses of the data in relation to the severity of plaque formation suggest that alterations in other neurochemical activities including reductions in dopamine-beta-hydroxylase activity, cholecystokinin octapeptide (aqueous extracted) and somatostatin immunoreactivities and an increase in substance P immunoreactivity, may occur at later stages of the disease process. These comparative data suggest that biochemical changes in this brain area associated with age and earlier stages of Alzheimer's disease may be relatively selective.
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PMID:Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes. 617 77

The concentration of substance P-like immunoreactive material (SPLI) and somatostatin-like immunoreactive material (SLI) and the activity of acetyl-CoA: choline-O-acetyltransferase (ChAT; EC 2.3.1.6) were measured in eight brain regions of 13 normal patients and 12 patients with Alzheimer disease/senile dementia of the Alzheimer type (AD/SDAT). SPLI was significantly lower in five of eight regions in the patients with AD/SDAT. Younger patients with AD/SDAT had significantly lower SLI in the parietal cortex than older patients. ChAT activity and SPLI in the parietal cortex of the presenile patients with AD/SDAT were not significantly different from values found in older patients.
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PMID:Cortical substance P-like immunoreactivity in cases of Alzheimer's disease and senile dementia of the Alzheimer type. 617 86


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