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)

A4 protein (beta-protein, beta-amyloid) deposits were identified with silver stains in postmortem brainstem sections from 13 patients with Alzheimer disease (AD), 6 patients with mixed Alzheimer disease and Parkinson disease (AD-PD), 5 disease controls, and 2 elderly controls. A rostro-caudal gradient of A4 was found in patients with AD and AD-PD, such that A4 was most prevalent in the midbrain and least prevalent in the medulla. The brainstem of the controls contained little or no A4. The midbrain tectum and tegmentum contained the greatest densities of A4, but the red nucleus and substantia nigra pars reticulata were largely spared. This distribution of A4 suggests that A4 deposition is a function of synaptic connectivity rather than passive diffusion from vascular sources.
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PMID:Distribution of amyloid in the brainstem of patients with Alzheimer disease. 130 Apr 98

Deposition of amyloid (A4) protein was assessed in the cerebral cortex of 26 patients dying with various neurodegenerative disorders, other than Alzheimer's disease. Amyloid deposits were (variably) present in 2/3 (66%) elderly (i.e. over 65 years of age) patients with progressive supranuclear palsy, 4/7 (57%) with Parkinson's disease, 2/5 (40%) with Huntington's chorea and in both elderly patients with frontal lobe dementia but were only rarely seen in any patient before this age. The A4 protein deposits were nearly always of a diffuse type with only an occasional 'cored' neuritic plaque being present. Amyloid deposition in elderly persons may thus relate more to certain aspects of ageing and genetics than to AD, per se. Only in this latter condition are the cerebral cortical amyloid deposits widely associated with a neuritic change and a neurofibrillary degeneration of nerve cells.
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PMID:Deposition of amyloid (A4) protein within the brains of persons with dementing disorders other than Alzheimer's disease and Down's syndrome. 213 61

The prevalence of deposition of the Alzheimer's disease A4 amyloid protein in representative areas of the cerebral cortex was compared using a sensitive immunohistochemical technique in a group of 26 cases of idiopathic Parkinson's disease (PD) and in a control group of 82 subjects of comparable age who had died unexpectedly from non-cerebral causes. Cortical A4 protein deposition was found in 54% of PD subjects and 48% of the control group, while deposition of A4 protein in meningeal or cortical blood vessels was found in 38% of PD subjects and 25% of controls. When allowance was made for age and sex, the differences between the two groups were not found to be statistically significant. Heavy cortical A4 protein deposition was found in a number of PD cases, including two of four cases with dementia, and was absent in the other two cases. The present findings indicate that a large proportion of cases of idiopathic PD have associated Alzheimer's disease changes. In some cases these lesions are of sufficient severity to account for dementia. In other cases the changes are less severe and are probably subclinical but may be a contributory factor to the development of cognitive impairment and dementia. The absence of Alzheimer changes in some demented PD cases indicates that the dementia of PD is heterogeneous.
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PMID:Deposition of Alzheimer's disease amyloid (A4) protein in the cerebral cortex in Parkinson's disease. 269 Jan 9

We have used biochemical assays to examine cingulate and occipital cortices from age-matched cases of Alzheimer's disease (AD; n = 12), senile dementia of the Lewy body type (SDLT; n = 13), Parkinson's disease (PD; 5 non-demented cases and 7 cognitively impaired cases) and controls (n = 11) for paired helical filaments (PHFs), phosphorylated and normal tau protein and beta/A4-protein. Whereas cingulate cortex is characterised by relatively high densities of cortical Lewy bodies in the SDLT cases and lower numbers in PD, these inclusion bodies were absent in the cingulate cortex from AD and control cases. Protease-resistant PHFs and hyperphosphorylated tau protein were found in AD and, at low levels, in a minority of SDLT cases. Qualitatively, both of these preparations were indistinguishable in SDLT from those found in AD but levels of both parameters in SDLT were less than 5% of those in AD. SDLT, PD and control groups did not differ from each other in terms of the quantity of protease-resistant PHFs or the level of hyperphosphorylated tau. Furthermore, PHF accumulation did not distinguish between PD cases with or without dementia. The levels of normal tau protein did not differ between the four groups. beta/A4 protein levels did not distinguish between PD and control groups, between AD and SDLT groups, or between SDLT and control groups for either cingulate or occipital cortices. Thus extensive accumulation of PHFs in either neurofibrillary tangles or dystrophic neurites is not a feature of either SDLT or PD. Our findings provide molecular support for the neuropathological and clinical separation of SDLT as a form of dementia that is distinct from AD.
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PMID:Senile dementia of Lewy body type and Alzheimer type are biochemically distinct in terms of paired helical filaments and hyperphosphorylated tau protein. 795 76

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

Alpha-synuclein is a presynaptic protein that is implicated in the pathogenesis of various neurodegenerative diseases. Missense mutations in the alpha-synuclein gene are linked to familial cases of Parkinson's disease (PD), and it has further been shown that alpha-synuclein is a major constituent of the Lewy bodies in sporadic PD and dementia with Lewy body (DLB). The contribution of alpha-synuclein to the pathological changes in Alzheimer's disease (AD) has been currently a matter of scientific debate. Some reports hypothesized that alpha-synuclein may play a role in amyloid beta/A4 protein (Abeta) aggregation in senile plaques, whereas recent reports challenged this finding by showing a lack of alpha-synuclein-immunoreactivity in Abeta plaques. In this review, we report on recent findings on the physiological and pathological role of alpha-synuclein and try to elucidate its possible contribution to AD pathology.
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PMID:Alpha-synuclein, Abeta and Alzheimer's disease. 1255 31

Alpha-synuclein is a pathological component of Parkinson's disease by constituting the filamentous component of Lewy bodies. Phthalocyanine (Pc) effects on the amyloidosis of alpha-synuclein have been examined. The copper complex of phthalocyanine tetrasulfonate (PcTS-Cu(2+)) caused the self-oligomerization of alpha-synuclein while Pc-Cu(2+) did not affect the protein, indicating that introduction of the sulfonate groups was critical for the selective protein interaction. The PcTS-Cu(2+) interaction with alpha-synuclein has occurred predominantly at the N-terminal region of the protein with a K(d) of 0.83 microM apart from the hydrophobic NAC (non-Abeta component of Alzheimer's disease amyloid) segment. Phthalocyanine tetrasulfonate (PcTS) lacking the intercalated copper ion also showed a considerable affinity toward alpha-synuclein with a K(d) of 3.12 microM, and its binding site, on the other hand, was located at the acidic C-terminus. These mutually exclusive interactions between PcTS and PcTS-Cu(2+) toward alpha-synuclein resulted in distinctive features on the kinetics of protein aggregation, morphologies of the final aggregates, and their in vitro cytotoxicities. The PcTS actually suppressed the fibrous amyloid formation of alpha-synuclein, but it produced the chopped-wood-looking protein aggregates. The aggregates showed rather low toxicity (9.5%) on human neuroblastoma cells (SH-SY5Y). In fact, the PcTS was shown to effectively rescue the cell death of alpha-synuclein overexpressing cells caused by the lactacystin treatment as a proteasome inhibitor. The anti-aggregative and anti-amyloidogenic properties of PcTS were also demonstrated with alcohol dehydrogenase, glutathione S-transferase, and amyloid beta/A4 protein under their aggregative conditions. The PcTS-Cu(2+), on the other hand, promoted the protein aggregation of alpha-synuclein, which gave rise to the fibrillar protein aggregates whose cytotoxicity became significant to 35.8%. Taken together, the data provided in this study indicate that PcTS/PcTS-Cu(2+) could be considered as possible candidates for the development of therapeutic or prophylactic strategies against the alpha-synuclein-related neurodegenerative disorders.
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PMID:Phthalocyanine tetrasulfonates affect the amyloid formation and cytotoxicity of alpha-synuclein. 1503 41