Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted an epitope analysis of senile plaque (SP) proteins on hippocampal SPs in patients with Parkinson's disease (PD), using a library of antibodies to proteins implicated in the genesis of hippocampal SPs in Alzheimer's disease (AD). The library included antibodies to the beta-amyloid protein (beta-AP), domains outside the beta-AP in beta-amyloid precursor proteins (beta-APPs), ubiquitin, diverse neuronal cytoskeletal proteins, and polypeptides located mainly in axon terminals. We obtained samples of hippocampus at autopsy from 14 PD patients, 10 of whom were demented. As in the AD hippocampus, the SPs detected by conventional stains in five of the 10 demented subjects contained the beta-AP and flanking domains in beta-APPs as well as epitopes in tau, neurofilament proteins, and synaptophysin. Further, with the exception of the beta-AP, epitopes in the other proteins were confined to the coronas of SPs, while clathrin light chain, microtubule-associated protein 5, and neural cell adhesion molecules were almost undetectable or absent in the neuropil occupied by SPs. The same group of antibodies rarely labeled SPs in the other five demented PD subjects or in the four nondemented PD subjects, and conventional stains for amyloid and neurofibrillary pathology revealed rare SPs in these cases. Hence, when conventional stains reveal lesions diagnostic of AD in PD patients, the molecular features of the hippocampal SPs in these patients are the same as those in SPs of the AD hippocampus.
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PMID:Epitope analysis of senile plaque components in the hippocampus of patients with Parkinson's disease. 137 4

Foamy spheroid bodies (FSBs) are described, as newly identified pathological structures occurring in human brain. FSBs favoured the substantia nigra pars reticulata (SNPR) and/or globus pallidus (GP) in degenerative conditions especially postencephalitic parkinsonism, progressive supranuclear palsy, pallido-nigro-luysial atrophy and multiple system atrophy. No FSBs were observed anywhere in the presence of substantia nigra pars compacta (SNPC) degeneration, such as occurs in idiopathic Parkinson's disease, or luysio-pallidal system degeneration, such as found in dentato-rubro-pallido-luysial atrophy or Joseph's disease. FSBs were also occasionally identified in the substantia nigra (SN) and/or GP of aged persons. In addition to SN and GP lesions, FSBs were seen in diffuse axonal lesions of long fibre tracts (the corpus callosum, the superior cerebellar peduncle) after non-missile head injuries, and in peri-infarct lesions. Under the light microscope, FSBs appear as slightly eosinophilic, foamy and nearly round objects with vague outlines, measuring approximately 10-50 microns in diameter. Some FSBs contain coarse, eosinophilic clusters at their periphery. FSB stained black when stained by the Gallyas silver method. Some FSBs were immunohistochemically positive for synaptophysin and 68 kDa neurofilament. Glial fibrillary acidic protein-positive fibres were observed alongside and/or inside some FSBs. Electron microscopically, FSBs were found to consist of collections of neuritic debris containing a variety of dense bodies and a small number of both mitochondria and neurofilaments. Some such collections were surrounded by astrocytic processes. These findings strongly suggest that FSBs are collections of small axonal debris destined for removal by astrocytes in due course. A variety of factors (degeneration of the SNPR and/or the GP, injury, infarction, ageing) seemed to be responsible for the histogenesis of FSBs.
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PMID:Peculiar axonal debris with subsequent astrocytic response (foamy spheroid body). A topographic, light microscopic, immunohistochemical and electron microscopic study. 155 16

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.
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PMID:Amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam: immunohistochemical studies. 158 17

This study was undertaken to evaluate the levels of cAMP-regulated phosphoproteins in the striatum of patients with neurodegenerative diseases of the dopaminergic system. Postmortem samples of caudate nucleus and putamen from 24 control subjects, 23 patients with Parkinson disease, and 13 patients with progressive supranuclear palsy were studied with immunoblotting techniques. The levels of tyrosine hydroxylase were reduced in patients with Parkinson disease (levels were 24% and 10% of controls in caudate nucleus and putamen, respectively) and with progressive supranuclear palsy (levels were 11% and 6% of controls in caudate nucleus and putamen, respectively). Five phosphoproteins, which are present in striatal neurons and are likely to play a role in the postsynaptic actions of dopamine, were measured. These included ARPP-16, ARPP-19, ARPP-21 (cAMP-regulated phosphoproteins of Mr 16,000, 19,000, and 21,000, respectively), DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32,000), and phosphatase inhibitor I. The levels of these phosphoproteins were inversely correlated with postmortem delay. In brains of patients with Parkinson disease or progressive supranuclear palsy with postmortem delays comparable to those of controls, the levels of these proteins as well as those of synaptic (synapsin I and synaptophysin) and glial (glial fibrillary acidic protein and myelin basic protein) markers were not significantly modified. We conclude that the levels of several phosphoproteins involved in signal transduction in striatal neurons are not altered in Parkinson disease and progressive supranuclear palsy. This observation supports the view that the striatal output neurons are intact in both diseases.
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PMID:Striatal phosphoproteins in Parkinson disease and progressive supranuclear palsy. 292 45

Both genetic and environmental factors affect the progression of Alzheimer's disease (AD). The presence of cortical Lewy bodies in AD patients is associated with an altered presentation of AD pathology suggestive of an interaction between the pathogenesis of Lewy bodies and AD lesions. Since the CYP2D6B mutant allele is often present in patients with Lewy body diseases (Parkinson's disease and Lewy body variant of AD), we extended these prior observations by studying the neuropathology associated with the presence of the CYP2D6B mutant allele in a pure AD population without Lewy bodies. AD patients who possessed the CYP2D6B mutant allele, in comparison with those without the CYP2D6B allele, were found to have a smaller decline in two synaptic markers, choline acetyltransferase and synaptophysin, in the frontal cortex relative to normal control values. On the other hand, senile plaques and neurofibrillary tangles were not significantly affected by the presence of the CYP2D6B mutant allele in the frontal cortex of AD patients. Association of the CYP2D6B mutant allele with Lewy body formation in both Parkinson's disease and the Lewy body variant of AD and with the milder synaptic pathology in pure AD without Lewy bodies suggest that depending on the contribution of other genetic and environmental factors, this mutant allele may be involved with different aspects of neurodegeneration.
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PMID:The CYP2D6B allele is associated with a milder synaptic pathology in Alzheimer's disease. 757 63

Lewy bodies commonly observed in brains with Parkinson's disease (PD) histochemically contain both protein and lipid as chemical components. Ultrastructurally, they are composed of filamentous, vesicular and granular structures. We investigated PD brains with light and electron microscopic immunohistochemistry using antibodies against two marker proteins for neuronal secretory vesicles, synaptophysin and chromogranin A. Both antibodies immunolabeled the peripheral zones and occasionally central cores of Lewy bodies of the classical and intraneuritic types. In addition, the diffuse immunolabeling was observed in Lewy bodies of the cortical type. Furthermore, the ultrastructural immuno-decoration was found mainly in the vesicular structures, and also in the filamentous and granular structures of Lewy bodies. Immuno-blot analysis of each antibody showed no difference between PD and normal control brains. The present observations suggest that vesicular profiles of Lewy bodies represent presynaptic and dense core secretory vesicles, and therefore that the lipid elements of Lewy bodies are derived from membrane lipids of these vesicles.
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PMID:Synaptophysin and chromogranin A immunoreactivities of Lewy bodies in Parkinson's disease brains. 813 Oct 84

We have examined the biochemical and histological effects of high concentrations of dopamine (0.05-1.0 micromol) injected into the rat striatum. Twenty-four hours after such injections, the oxidation products of dopamine and dihydroxyphenylacetic acid were detected as both free and protein-bound cysteinyl dopamine and cysteinyl dihydroxyphenylacetic acid. Protein-bound cysteinyl catechols were increased 7- to 20-fold above control tissue levels. By 7 days postinjection, the protein-bound cysteinyl catechols were still detectable, although reduced in concentration, whereas the free forms could no longer be measured. Histological examination of striatum at 7 days revealed a central core of nonspecific damage including neuronal loss and gliosis. This core was surrounded by a region containing a marked reduction in tyrosine hydroxylase immunoreactivity but no apparent loss of serotonin or synaptophysin immunoreactivity. When dopamine was injected with an equimolar concentration of either ascorbic acid or glutathione, the formation of protein-bound cysteinyl catechols was greatly reduced. Moreover, the specific loss of tyrosine hydroxylase immunoreactivity associated with dopamine injections was no longer detectable, although the nonspecific changes in cytoarchitecture were still apparent. Thus, following its oxidation, dopamine in high concentrations binds to protein in the striatum, an event that is correlated with the specific loss of dopaminergic terminals. We suggest that the selective degeneration of dopamine neurons in Parkinson's disease may be caused by an imbalance between the oxidation of dopamine and the availability of antioxidant defenses.
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PMID:Role of oxidation in the neurotoxic effects of intrastriatal dopamine injections. 870 Aug 66

The precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP) (also known as a-synuclein) is a presynaptic terminal molecule that accumulates in the plaques of Alzheimer's disease. Recent studies have shown that a mutation in NACP is associated with familial Parkinson's disease, and that Lewy bodies are immunoreactive with antibodies against this molecule. To clarify the patterns of accumulation and differences in abnormal compartmentalization, we studied NACP immunoreactivity using double immunolabeling and laser scanning confocal microscopy in the cortex of patients with various neurodegenerative disorders. In Lewy body variant of Alzheimer's disease, diffuse Lewy body disease, and Parkinson's disease, NACP was found to immunolabel cortical Lewy bodies, abnormal neurites, and dystrophic neurites in the plaques. Double-labeling studies showed that all three of these neuropathological structures also contained ubiquitin, synaptophysin, and neurofilament (but not tau) immunoreactivity. In contrast, neurofibrillary tangles, neuropil threads, Pick bodies, ballooned neurons, and glial tangles (most of which were tau positive) were NACP negative. These results support the view that NACP specifically accumulates in diseases related to Lewy bodies such as Lewy body variant of Alzheimer's disease, diffuse Lewy body disease, and Parkinson's disease and suggests a role for this synaptic protein in the pathogenesis of neurodegeneration.
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PMID:Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders. 946 62

The non-Abeta component of Alzheimer's disease amyloid precursor protein (NACP) is predominantly a neuron-specific presynaptic protein that may play a central role in neurodegeneration because NACP fragments are found in Alzheimer's disease amyloid and a mutation in the NACP gene is associated with familial Parkinson's disease. In addition, NACP may play an important role during synaptogenesis and CNS development. To understand better the patterns of NACP expression during development, we analyzed the levels of this protein as well as the levels of another synaptic protein (synaptophysin) by ribonuclease protection assay, western blotting, and immunocytochemistry in fetal, juvenile, and adult mouse brain. From embryonic day 12 to 15, there was a slight increase, which was then followed by a more dramatic increase at later time points. Immunocytochemical staining for NACP increases throughout these stages as well. Although NACP appeared early in CNS development, synaptophysin levels started to rise at a later stage. These findings support the contention that NACP might be important for CNS development. Furthermore, the cytosolic component of NACP precedes the particulate component in development, indicating that a redistribution of the protein to the membrane fraction may be important for events later in neuronal development and in synaptogenesis.
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PMID:Expression pattern of synucleins (non-Abeta component of Alzheimer's disease amyloid precursor protein/alpha-synuclein) during murine brain development. 964 83

Synucleins are abundant nerve terminal proteins of hitherto unknown function. In diseases with Lewy bodies, human alpha-synuclein concentrates in these lesions in the cell body and mutations in alpha-synuclein lead to heritable Parkinson's disease with Lewy bodies. This indicates that changes in the normal metabolism and axonal transport of alpha-synuclein is perturbed in these diseases. To investigate the normal axonal transport of synucleins we studied the rat visual system by nerve crush operations and metabolic labelling of the retinal ganglion cells followed by immunoprecipitation of nerve segments. We found by immunofluorescence microscopy of the crush-operated nerves that synucleins are transported by fast antero- and retrograde transport and colocalize with synaptophysin and SNAP-25 around the lesion. The metabolic labelling studies demonstrated that synucleins were moved through the nerve with all the rate components, the fast component and the slow components a and b, with component b predominating. Two-dimensional gel electrophoresis revealed that both alpha- and beta-synuclein migrate through the nerve by slow component b in a ratio of 2:1.
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PMID:Axonal transport of synucleins is mediated by all rate components. 1056 44


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