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)

Deposition of fibrillar amyloid beta protein (A beta) is increased in brains of patients with Alzheimer's disease. Concentrations of A beta were measured in cerebrospinal fluid with an enzyme-linked immunosorbent assay in 10 neurological patients free from neurodegenerative disease, 28 patients with Parkinson's disease, and 18 patients with probable Alzheimer's disease. Levels of A beta in cerebrospinal fluid were not significantly different among these groups. This observation suggests that concentrations of soluble A beta in cerebrospinal fluid as measured in this study do not reflect the amount of fibrillar, aggregated A beta in the brain of patients with Alzheimer's disease.
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PMID:Concentrations of amyloid beta protein in cerebrospinal fluid of patients with Alzheimer's disease. 784 70

It is not known whether an increased incidence of dementia in patients with Parkinson's disease (PD) is due to a higher incidence of Alzheimer's disease (AD) or to "early" Alzheimer-type pathology. To determine whether amyloid beta-peptide (A beta) of AD occurs more frequently in brains of patients with PD, we examined 50 cases and 79 controls by using histoblots for A beta. Twenty-three cases with PD had dementia, including all nine with A beta distributed throughout the entire cerebral cortex; three of these cases had AD. In contrast, five of 17 controls with comparable A beta accumulation were not demented. Neither AD nor A beta deposition was increased in PD, furthermore, there was no statistical correlation between the amount of A beta and the number of Lewy bodies in cerebral cortex. In 14 patients with PD in whom dementia was unrelated to A beta, there was cerebral vascular disease (four), numerous cortical Lewy bodies (three), or hydrocephalus (two); in five further cases, dementia was not well explained by histopathologic changes. Our data found no increase of either AD or "early" Alzheimer-type pathology in cases of PD; however, a synergistic effect between the two pathologies was suggested as contributing to dementia.
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PMID:Amyloid beta-peptide and the dementia of Parkinson's disease. 891 90

Oxidative stress is believed to play important roles in neuronal cell death associated with many different neurodegenerative conditions (e.g., Alzheimer's disease, Parkinson's disease, and cerebral ischemia), and it is believed also that apoptosis is an important mode of cell death in these disorders. Membrane lipid peroxidation has been documented in the brain regions affected in these disorders as well as in cell culture and in vivo models. We now provide evidence that 4-hydroxynonenal (HNE), an aldehydic product of membrane lipid peroxidation, is a key mediator of neuronal apoptosis induced by oxidative stress. HNE induced apoptosis in PC12 cells and primary rat hippocampal neurons. Oxidative insults (FeSO4 and amyloid beta-peptide) induced lipid peroxidation, cellular accumulation of HNE, and apoptosis. Bcl-2 prevented apoptosis of PC12 cells induced by oxidative stress and HNE. Antioxidants that suppress lipid peroxidation protected against apoptosis induced by oxidative insults, but not that induced by HNE. Glutathione, which binds HNE, protected neurons against apoptosis induced by oxidative stress and HNE. PC12 cells expressing Bcl-2 exhibited higher levels of glutathione and lower levels of HNE after oxidative stress. Collectively, the data identify that HNE is a novel nonprotein mediator of oxidative stress-induced neuronal apoptosis and suggest that the antiapoptotic action of glutathione may involve detoxification of HNE.
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PMID:Evidence that 4-hydroxynonenal mediates oxidative stress-induced neuronal apoptosis. 918 46

The distribution of amyloid beta peptide (A beta) was quantified in the corpus striatum and pallidum of 10 patients with Alzheimer's disease (AD) and three patients with both Alzheimer's disease and Parkinson's disease (AD-PD). A beta occurred almost exclusively in plaques that did not have neurites or amyloid cores. Caudate, accumbens nuclei and rostral putamen contained more of the diffuse plaques than did caudal putamen. No diffuse plaques were found in the neighbouring globus pallidus. This distribution of A beta deposition may reflect the distribution of diseased synaptic cortical afferents rather than a putative vascular source of A beta.
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PMID:The distribution of amyloid beta protein deposition in the corpus striatum of patients with Alzheimer's disease. 929 71

Cerebral cortical Lewy bodies occur in a spectrum of clinical syndromes including Parkinson's disease (PD) with and without dementia, and dementing conditions clinically resembling Alzheimer's disease with few or without parkinsonian features. It is unclear whether these conditions are variants of one disease process or represent pathogenetically distinct entities. Here we compared the cortical pathology in post mortem brains of three groups representing the predominant clinical phenotypes of Lewy body disease, including 27 non-demented cases of PD, 23 demented PD cases, and 11 cases of Lewy body disease who initially presented with dementia and showed only limited features of parkinsonism during the course of their illness. In addition to neuropathology, computer-assisted histoblot analysis was used to assess cortical amyloid beta-peptide deposition. There was wide overlap of the pathomorphometric features between the two groups of demented cases. It appears that substantial cortical Alzheimer-type pathology present in most demented cases contributes significantly to the development of dementia in Lewy body disease.
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PMID:Amyloid beta-peptide and its relationship with dementia in Lewy body disease. 947 Jan 34

The precursor of non-amyloid beta protein component of Alzheimer's disease amyloid (NACP/alpha-synuclein) is aggregated and fibrillated under certain conditions, i.e., increasing time lag, high temperature and low pH. These in vitro aggregates form Thioflavine-S-positive filamentous structures, reminiscent of amyloid-like fibrils. Since some Lewy bodies in Parkinson's disease display Thioflavine-S reactivity, our results may suggest that amyloidogenic properties of NACP/alpha-synuclein may play a crucial role in pathogenesis of disorders with Lewy bodies such as Parkinson's disease.
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PMID:Human recombinant NACP/alpha-synuclein is aggregated and fibrillated in vitro: relevance for Lewy body disease. 967 19

Melatonin was recently reported to be an effective free radical scavenger and antioxidant. Melatonin is believed to scavenge the highly toxic hydroxyl radical, the peroxynitrite anion, and possibly the peroxyl radical. Also, secondarily, it reportedly scavenges the superoxide anion radical and it quenches singlet oxygen. Additionally, it stimulates mRNA levels for superoxide dismutase and the activities of glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase (all of which are antioxidative enzymes), thereby increasing its antioxidative capacity. Also, melatonin, at least at some sites, inhibits nitric oxide synthase, a pro-oxidative enzyme. In both in vivo and in vitro experiments melatonin has been shown to reduce lipid peroxidation and oxidative damage to nuclear DNA. While these effects have been observed primarily using pharmacological doses of melatonin, in a small number of experiments melatonin has been found to be physiologically relevant as an antioxidant as well. The efficacy of melatonin in inhibiting oxidative damage has been tested in a variety of neurological disease models where free radicals have been implicated as being in part causative of the condition. Thus, melatonin has been shown prophylactically to reduce amyloid beta protein toxicity of Alzheimer's disease, to reduce oxidative damage in several models of Parkinson's disease (dopamine auto-oxidation, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine), to protect against glutamate excitotoxicity, to reduce ischemia-reperfusion injury, to lower neural damage due to gamma-aminolevulinic acid (phorphyria), hyperbaric hyperoxia and a variety of neural toxins. Since endogenous melatonin levels fal 1 markedly in advanced age, the implication of these findings is that the loss of this antioxidant may contribute to the incidence or severity of some age-associated neurodegenerative diseases.
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PMID:Oxidative damage in the central nervous system: protection by melatonin. 977 Feb 44

The precursor of non-amyloid beta protein component of Alzheimer's disease amyloid (NACP/alpha-synuclein), found in Lewy bodies of Parkinson's disease (PD), is a presynaptic protein genetically linked to some familial types PD. Mechanisms of abnormal NACP/alpha-synuclein aggregation in neurodegenerative diseases are unclear. Since oxidative stress might play a role in PD pathogenesis, we investigated the role of iron and peroxide in NACP/alpha-synuclein aggregation. Immunoblot analysis showed that human NACP/alpha-synuclein (but not beta-synuclein) aggregated in the presence of ferric ion and was inhibited by the iron chelator deferoxamine. Ferrous ion was not effective by itself, but it potentially aggregated NACP/alpha-synuclein in the presence of hydrogen peroxide. NACP/ alpha-synuclein aggregates displayed strong thioflavine-S and congo-red reactivity, reminiscent of amyloid. This study suggests that NACP/alpha-synuclein aggregation might be closely related to oxidative reactions which may play a critical role in neurodegeneration in disorders with Lewy bodies.
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PMID:Oxidative stress induces amyloid-like aggregate formation of NACP/alpha-synuclein in vitro. 1020 37

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

The precursor of the non-amyloid beta/A4 protein (non-Abeta) component of Alzheimer's disease amyloid (NACP)/alpha-synuclein is the human homologue of alpha-synuclein, a member of a protein family which includes alpha-, beta- and gamma-synuclein. This protein is thought to be involved in neuronal plasticity because of its unique expression, mainly in the telencephalon during maturation. Consequently, disarrangement of NACP/alpha-synuclein might disrupt synaptic activity, resulting in memory disturbance. Previous studies have shown that damage to synaptic terminals is closely associated with global cognitive impairment and is an early event in the pathogenesis of Alzheimer's disease. Although the relationship between synaptic damage and amyloidogenesis is not clear, some proteins at the synaptic site have been implicated in both neuronal alteration and amyloid formation. Indeed, abnormal accumulation of both NACP/alpha-synuclein and Abeta precursor protein occurs at synapses of Alzheimer's patients. Other evidence suggests that NACP/alpha-synuclein is a component of the Lewy bodies found in patients with Parkinson's disease or dementia with Lewy bodies, and that a point mutation in this protein may be the cause of familial Parkinson's disease. Consequently, abnormal transport, metabolism or function of NACP/alpha-synuclein appears to impair synaptic function, which induces, at least in part, neuronal degeneration in several neurodegenerative diseases.
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PMID:Properties of NACP/alpha-synuclein and its role in Alzheimer's disease. 1089 35


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