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

Neuronal death associated with plaque and tangle formation characteristic of Alzheimer's disease (AD) may result from an underlying defect of intracellular protein catabolism. In an attempt to identify the proteolytic enzyme types responsible for aberrant protein processing, we have composed the levels of activity of proline endopeptidase in brain tissue samples (grey/white matter) from frontal, parietal, temporal and occipital lobes, from normal control cases, and cases with AD, Lewy body dementia (LBD), Parkinson's disease (PD) and Huntington's disease (HD). The activity of proline endopeptidase was significantly reduced in AD to approximately 65% of that of corresponding control tissue-this is of note since previous biochemical analyses have in general failed to detect altered activity of other protease types in AD tissues. However, this relatively selective reduction in proline endopeptidase activity in AD tissue (in terms of protease types investigated) is not specific for disease type, since activity was also reduced (65%-70% of control) in tissue samples from LBD, PD and HD cases. The data suggest that reduction in proline endopeptidase activity may be a characteristic of a generalized process of neurodegeneration. Although the precise cellular function of this enzyme in normal/ pathological tissues remains to be determined, the question arises as to whether pharmacological strategies designed to enhance proline endopeptidase activity in brain tissue may improve patient outcome in the above disorders.
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PMID:Comparison of proline endopeptidase activity in brain tissue from normal cases and cases with Alzheimer's disease, Lewy body dementia, Parkinson's disease and Huntington's disease. 873 97

Lewy bodies (LBs)are found throughout the brain stem, limbic and neocortical areas in Parkinson's disease. Lewy bodies are also associated in these areas with dementia and the substrate of 'dementia with Lewy bodies' is thought to include Lewy body pathology in limbic and neocortical areas with or without Alzheimer-type changes. In order to determine whether dementia with Lewy bodies is characterised primarily by cortical or limbic LB pathology, we have measured the density of Lewy bodies, neuritic plaques and neurofibrillary tangles in 12 neocortical, limbic and brain stem sites in 10 patients who were pathologically diagnosed with diffuse Lewy body disease (DLBD) (64.7 +/- 2.7 years). The mean LB density in limbic areas (3.00 +/- 0.61/mm2) was significantly greater than that of neocortical areas (1.13 +/- 0.22/mm2, P < 0.001). The greatest density of LBs was found in the amygdala (4.1 +/- 0.7/mm2) and the lowest in the occipital cortex (0.3 +/- 0.1/mm2). In limbic areas, LB formation positively correlated with neuritic plaque formation (r = 0.51, P < 0.01) but not with neurofibrillary tangle densities. These data indicate that dementia with Lewy bodies is characterised primarily by limbic, and secondly by neocortical, LB pathology. It remains to be determined why limbic areas are selectively vulnerable to LB pathology in dementia with Lewy bodies.
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PMID:Lewy bodies are located preferentially in limbic areas in diffuse Lewy body disease. 883 51

The scanning nuclear microprobe (nuclear microscope) is becoming a powerful instrument for the accurate measurement of minor and trace elements in biological tissue. Using the simultaneously applied techniques of Scanning Transmission Ion Microscopy (STIM) to image features in the tissue, Particle induced X-ray emission (PIXE) to measure trace element concentrations, and Rutherford Backscattering Spectrometry (RBS) to characterize the tissue matrix, accurate elemental analysis at the parts per million level can be obtained for most elements. This review describes briefly the results obtained using the nuclear microscope for the elemental analysis of Alzheimer's and Parkinson's tissue. In Alzheimer's disease (AD) the identification and subsequent analysis of neuritic plaque cores in unstained tissue, yielded an absence of aluminium at the limit of 15 parts per million. Previous analyses involving stained sections were prone to misinterpretation due to aluminium contamination from the staining procedures. Elemental iron, calcium, phosphorus and sulphur were elevated both in the plaques and the AD background tissue compared to age matched controls. Preliminary analyses of neurofibrillary tangles stained with toluidine blue showed increased levels of calcium, although the staining procedure may have distorted the results due to element redistribution. In Parkinson's disease (PD) nuclear microscope studies have concentrated on measurements of iron in the substantia nigra (SN) region of the brain; iron was observed to be elevated by a factor 2 in MPTP induced Parkinsonism in African Green monkeys, and by a factor of 1.25 in 6-OHDA induced Parkinsonism in Sprague Dawley rats. These studies are consistent with other studies showing a general increase in the concentrations of iron associated with PD, and support the theory that iron mediated free radical production may enhance or accelerate the degeneration of dopaminergic cells through oxidative stress.
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PMID:Nuclear microscope analysis in Alzheimer's and Parkinson's disease: A review. 883 63

Omental transposition (OT) to revascularize the brain was first performed in animals in the late 1960s, where it was shown that blood vessels originating from the omentum crossed through the omental-cerebral interface prior to developing into large-sized vessels that penetrated directly and deeply into the underlying brain. The additional cerebral blood flow coming from the omentum was of sufficient volume to protect an animal's brain from cerebral infarction even in the presence of middle cerebral artery ligation. It was also learned that the omentum was a rich source for neurotransmitters and omentum-derived nerve growth substance. OT to the brain is now being done for a variety of conditions which include strokes, TIAs, epilepsy, and Parkinson's disease. Of recent interest is the published information that OT may play some role in Alzheimer's disease (AD). The placement of the omentum on an AD brain has led to a profound decrease in senile plaque formation. The omentum may ultimately prove to be beneficial in reversing or at least stabilizing the dementia associated with the devastation of AD.
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PMID:Omental transposition to the brain for Alzheimer's disease. 932 3

CERAD, a multicenter longitudinal study, has developed standardized instruments for the evaluation of individuals clinically diagnosed as having Alzheimer's disease (AD). The CERAD neuropathology protocol not only establishes levels of certainty for AD diagnosis, but also records information on other conditions occurring concomitantly with or misdiagnosed as AD. The protocol has been widely adopted because of its relative simplicity, adaptability, and reliability. Indeed, the Consensus principles proposed are, for the most part, consistent with CERAD guidelines. The recommendation that diagnosis rest upon both neuritic plaque and neurofibrillary tangle frequency/distribution in the neocortex, however, is worrisome. This change will eliminate or downgrade many cases now diagnosed as AD with concomitant Parkinson's disease changes. Reclassifying such cases at this time, without compelling pathobiological justification, is premature. Instead, I recommend retention or modest modification of the current CERAD protocol, and propose that neuropathology data available on autopsies of over 200 CERAD dementia subjects be used for testing potential modifications of the diagnostic algorithm.
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PMID:The CERAD neuropathology protocol and consensus recommendations for the postmortem diagnosis of Alzheimer's disease: a commentary. 933 Sep 94

To elucidate whether the apolipoprotein E epsilon4 allele (APOE4) affects cortical neuropathology in Parkinson's disease (PD), we determined APOE genotypes and quantified the densities of cortical Lewy bodies (LBs), amyloid plaques and neurofibrillary tangles in 22 autopsy-proven PD cases (12 with dementia; 10 without dementia) that were not accompanied by Alzheimer's disease. The APOE4 frequency in the demented patient group was 0.21, which was significantly higher than that in Japanese controls (P < 0.04). LB densities in demented PD patients were significantly higher than those in non-demented PD patients, despite the shorter disease duration in the former. Moreover, plaque density in the temporal cortex and LB density in the cingulate cortex were significantly higher in the group with APOE4 than in that without the allele. There was no difference in tangle density between these two groups. These results suggest that APOE4 may influence the increase in the number of cortical LBs and amyloid plaques in PD. It is possible that when PD occurs in individuals with APOE4, concomitantly evolving cortical LB pathology in a proportion of cases results in limbic (transitional) or neocortical-type LB disease.
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PMID:Apolipoprotein E epsilon4 allele and progression of cortical Lewy body pathology in Parkinson's disease. 960 May 90

In the last decade, a new degenerative dementia, probably the second most common after Alzheimer's disease (AD), has been increasingly recognized under the consensus name of dementia with Lewy bodies (DLB). This article reviews current clinical, genetic, and pathological DLB data and indicates directions for future research. DLB overlaps in clinical, pathological, and genetic features with AD and Parkinson's disease (PD). Clinically, it is characterized by progressive cognitive impairment with significant fluctuations in alertness, parkinsonism, and psychosis with recurrent hallucinations. The neuropathological hallmarks are the intracytoplasmic inclusions in substantia nigra typical of PD, known as Lewy bodies (LB) but distributed widely throughout paralimbic and neocortical regions. Most of the cases also coexist with a plaque predominant AD. It is probably the unique and differential distribution of the lesions throughout cortical and subcortical structures in each of these disorders that supports a specific clinical syndrome and may ultimately prove most useful in understanding their different etiologies. Several genes have recently been implicated in LB formation. Special interest arises from mutations in the alpha-synuclein gene, which appears to be responsible for autosomal dominant PD in several kindreds. This gene encodes a presynaptic protein, a fragment of which is present in AD plaques. Recent studies show intense and quite specific alpha-synuclein immunoreactivity in LB and related neurites, suggesting a potential role of this protein in the aggregation or precipitation of LB inclusions.
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PMID:Dementia with Lewy bodies. 980 70

alpha-Synuclein is a component of the abnormal protein depositions in senile plaques and Lewy bodies of Alzheimer's disease (AD) and Parkinson's disease respectively. The protein was suggested to provide a possible nucleation centre for plaque formation in AD via selective interaction with amyloid beta/A4 protein (Abeta). We have shown previously that alpha-synuclein has experienced self-oligomerization when Abeta25-35 was present in an orientation-specific manner in the sequence. Here we examine this biochemically specific self-oligomerization with the use of various metals. Strikingly, copper(II) was the most effective metal ion affecting alpha-synuclein to form self-oligomers in the presence of coupling reagents such as dicyclohexylcarbodi-imide or N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline. The size distribution of the oligomers indicated that monomeric alpha-synuclein was oligomerized sequentially. The copper-induced oligomerization was shown to be suppressed as the acidic C-terminus of alpha-synuclein was truncated by treatment with endoproteinase Asp-N. In contrast, the Abeta25-35-induced oligomerizations of the intact and truncated forms of alpha-synuclein were not affected. This clearly indicated that the copper-induced oligomerization was dependent on the acidic C-terminal region and that its underlying biochemical mechanism was distinct from that of the Abeta25-35-induced oligomerization. Although the physiological or pathological relevance of the oligomerization remains currently elusive, the common outcome of alpha-synuclein on treatment with copper or Abeta25-35 might be useful in understanding neurodegenerative disorders in molecular terms. In addition, abnormal copper homoeostasis could be considered as one of the risk factors for the development of disorders such as AD or Parkinson's disease.
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PMID:Copper(II)-induced self-oligomerization of alpha-synuclein. 1035 69

Recently several responsible genes for hereditary neurodegenerative disorders were identified. In some of them the gene products were found to be aggregated. In the case of Alzheimer disease beta protein and apolipoprotein E accumulated in senile plaques. In CAG repeat diseases the polyglutamine aggregates in neuronal nuclei. More recently alpha synuclein accumulates in Lewy bodies in Parkinson disease and tau protein accumulates in NFT of hereditary frontotemporal dementia with tau mutation. Those results suggested that the responsible gene products accumulates in the lesion which the products involve in. However, presenilin which is one of the genes for familial Alzheimer disease accumulates in NFT and on the other hand its mutation changes the production ratio of beta 1-42/40, suggesting that the abnormal gene products not simply accumulate the lesion that it involved. The gene products accumulate in different lesions such as in nuclei of polyglutamine diseases, extracellular plaque and cytoplasm of prion disease and extracellular plaques in Alzheimer disease. Some of them are ubiquitinated and some of them are not. Thus the accumulating process in these disorders seems apparently same but is essentially different. We should study more precisely each pathological process of those disorders.
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PMID:[Neuronal cell death--what we can see and what we cannot]. 1037 83

Alzheimer's disease (AD) and Lewy body disease (LBD) are the most common causes of dementia in the elderly population. Previous studies have shown that cognitive alterations in these disorders are associated with synaptic loss. Injury and loss of synapses might be associated with altered function of synaptic proteins. Among them, recent studies have shown that abnormal aggregation and accumulation of synaptic proteins, such as alpha-synuclein, might be associated with plaque formation in AD and Lewy body formation in LBD. Further reinforcing the hypothesis that alpha-synuclein plays a major role in the pathogenesis of these disorders, recent work has shown that mutations that alter the conformation of this molecule are associated with familial forms of Parkinson's disease. The mechanisms by which altered function or aggregation of alpha-synuclein might lead to neurodegeneration are not completely clear; however, new evidence points to a potential role for this molecule in synaptic damage and neurotoxicity via amyloid-like fibril formation and mitochondrial dysfunction. In this manuscript we review the data linking alpha-synuclein to the pathogenesis of AD and LBD.
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PMID:Alpha-synuclein in Lewy body disease and Alzheimer's disease. 1051 9


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