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)

Movement disorders presenting with parkinsonism may share histopathological features with Creutzfeldt-Jakob disease, a spongiform encephalopathy caused by the accumulation of pathological prion protein in brain. To investigate a possible aetiological link between these conditions and Creutzfeldt-Jakob disease, histoblot immunostaining for pathological prion protein was carried out in 90 cases including idiopathic Parkinson's disease, multiple system atrophy, diffuse Lewy body disease, Steele-Richardson-Olszewski syndrome, corticobasal degeneration, and Pick's disease. Pathological prion protein was identified in four controls with Creutzfeldt-Jakob disease but not in any of the other diseases examined. The findings suggest that an aetiological role for prions in these movement disorders is unlikely. Histoblotting provides a useful method for screening large areas of tissue for the presence of pathological prion protein and may be helpful in the differential diagnosis of difficult cases.
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PMID:Absence of disease related prion protein in neurodegenerative disorders presenting with Parkinson's syndrome. 793 89

The purpose of this study is to present a hypothesis to explain the aetiology of bovine spongiform encephalopathy (BSE) which is more credible than any at present available, and to increase its credibility by varying the hypothesis to supply explanations for Alzheimer's disease, Parkinson's disease and certain other conditions. The method used has been to utilize material from biochemical textbooks and similar sources. It has been concluded that BSE is caused by the failure to synthesize sufficient cyclic guanosine monophosphate (cGMP), with the result that neurons die because they are no longer able to prevent the entry of toxic quantities of calcium ions into their cytoplasm. Several causes for the failure to synthesize sufficient cGMP have been identified; these involve selenium and folate deficiencies, and problems with the availability of nicotinamide adenosine dinucleotide (NAD). It is proposed that BSE is initiated by a combination of selenium deficiency and the destruction of NAD by a bacterial toxin of the same type as causes cholera, that folate deficiency is the predominant cause of Alzheimer's disease, and that the failure to synthesize sufficient tetrahydrobiopterin and cGMP from guanosine triphosphate results in Parkinson's disease.
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PMID:A biochemical theory to explain the cause of bovine spongiform encephalopathy and other encephalopathies. 1139 7

Transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative diseases of humans and animals, including bovine spongiform encephalopathy (BSE) of cattle, scrapie of sheep, and Creutzfeldt-Jakob disease (CJD) of humans. Prion diseases have become an important issue in public health and in the scientific world not only due to the possible relationship between BSE and new variant CJD (nvCJD) but also due to the unique biological features of the infectious agent. Although the nature of the infectious agent and the pathogenic mechanisms of prion diseases are not fully understood, considerable evidence suggests that an abnormal form (PrP(Sc)) of a host prion protein (PrP(C)) may compose substantial parts of the infectious agent and that various factors such as oxidative stress and calcium cytotoxicity are associated with the pathogenesis of prion diseases. Here, we briefly review and discuss the pathogenic mechanisms of prion diseases. These advances in understandings of fundamental biology of prion diseases may open the possibilities for the prevention and treatment of these unusual diseases and also suggest applications in more common neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD).
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PMID:The pathogenic mechanisms of prion diseases. 1247 Sep 1

Recent investigations of scrapie, Creutzfeldt-Jakob disease (CJD), and chronic wasting disease (CWD) clusters in Iceland, Slovakia and Colorado, respectively, have indicated that the soil in these regions is low in copper and higher in manganese, and it has been well-known that patients of ALS or Parkinson's disease were collectively found in the New Guinea and Papua islands, where the subterranean water (drinking water) contains much Al3+ and Mn2+ ions. Above facts suggest that these neurodegenerative diseases are closely related with the function of a metal ion. We have investigated the chemical functions of the metal ions in detail and established the unique mechanism of the oxygen activation by the transition metal ions such as iron and copper, and pointed out the notable difference in the mechanism among iron, aluminum and manganese ions. Based on these results, it has become apparent that the incorporation of Al(III) or Mn(II) in the cells induces the "iron-overload syndrome", which is mainly due to the difference in an oxygen activation mechanism between the iron ion and Al(III) or the Mn(II) ion. This syndrome highly promotes formation of hydrogen peroxide, and hydrogen peroxide thus produced can be a main factor to cause serious damages to DNA and proteins (oxidative stress), yielding a copper(II)- or manganese(II)-peptide complex and its peroxide adduct, which are the serious agents to induce the structural changes from the normal prion protein (PrP(c)) to abnormal disease-causing isoforms, PrP(Sc), or the formation of PrP 27-30 (abnormal cleavage at site 90 of the prion protein). It seems reasonable to consider that the essential origin for the transmissible spongiform encephalopathies (TSEs) should be the incorporation and accumulation of Al(III) and Mn(II) ions in the cells, and the sudden and explosive increase of scrapie and bovine spongiform encephalopathy (BSE) in the last decade may be partially due to "acid rain", because the acid rain makes Al(III) and Mn(II) ions soluble in the subterranean aquifers.
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PMID:Elucidation of endemic neurodegenerative diseases--a commentary. 1457 44

The family of illnesses called transmissible spongiform encephalopathies (TSEs), or "prion" diseases, is composed of a small number of human and animal neurodegenerative diseases caused by unique pathogenic agents that are still not fully defined. They are best considered as "protein-misfolding diseases" (together with Alzheimer's disease, Parkinson's disease, and a few other rare examples) resulting from the conversion of a normal body protein into a misfolded amyloid multimer. The pathogenic agents display a unique resistance to conventional disinfection methods and an extraordinary environmental durability, which has led the US Department of Agriculture to designate the causative agent of bovine spongiform encephalopathy as a bioterrorism security threat. In this review, precautions and regulations concerning the handling of TSE agents are discussed in relation to personnel and environmental biosafety.
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PMID:Working with transmissible spongiform encephalopathy agents. 1564 63

Optical contrast is often the limiting factor in the imaging of live biological tissue. Studies were conducted in postmortem human brain to identify clinical applications where the structures of interest possess high intrinsic optical contrast and where the real-time, high-resolution imaging capabilities of optical coherence tomography (OCT) may be critical. Myelinated fiber tracts and blood vessels are two structures with high optical contrast. The ability to image these two structures in real time may improve the efficacy and safety of a neurosurgical procedure to treat Parkinson's disease called deep brain stimulation (DBS). OCT was evaluated as a potential optical guidance system for DBS in 25 human brains. The results suggest that catheter-based OCT has the resolution and contrast necessary for DBS targeting. The results also demonstrate the ability of OCT to detect blood vessels with high sensitivity, suggesting a possible means to avoid their laceration during DBS. Other microscopic structures in the human brain with high optical contrast are pathological vacuoles associated with transmissible spongiform encephalopathy (TSE). TSE include diseases such as Mad Cow disease and Creutzfeldt-Jakob disease (CJD) in humans. OCT performed on the brain from a woman who died of CJD was able to detect clearly the pathological vacuoles.
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PMID:Optical coherence tomography in the diagnosis and treatment of neurological disorders. 1629 51

Use of microencapsulation technology in combination with absorption enhancers eliminated epithelium irritation and necrosis commonly associated with nasal delivery of cytotoxic therapeutic agents. Phenothiazines, such as ethopropazine (ETZ), promethazine, trimeprazine and propiomazine have been used for the treatment of allergenic conditions, motion sickness, nausea, Parkinson's disease, Prion disease and as a sedative for psychiatric disorders. The enantiomers of commercially available racemic phenothiazines were isolated and purified using classical diastereomeric salt techniques. The racemate and the enantiomers of ETZ were tested in vitro for their cellular toxicity using lung fibroblast cells. Each enantiomer was shown to be cytotoxic at concentrations greater than 10(-5) molar. The ETZ enantiomers were encapsulated using spinning disk atomization to prepare a nasal delivery dosage form that does not produce an irritation response. Release rates for the ETZ microcapsules were determined in vitro and an animal study was conducted to determine the irritation response of rat nasal mucosa when dosed with encapsulated vs. non-encapsulated ETZ.
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PMID:Mucosal delivery of cytotoxic therapeutic agents: response of rat nasal mucosa to microencapsulated ethopropazine HCl enantiomer. 1642 Oct 84

Prion diseases for the most part affect individuals older than 60 years of age and share features with other diseases characterized by protein deposits in the brain, such as Alzheimer's disease and Parkinson's disease. The international conference "Prion 2005: Between Fundamentals and Society's Needs," organized by the German Transmissible Spongiform Encephalopathies Research Platform, aimed to integrate and coordinate the research efforts of participants to better achieve prevention, treatment, control, and management of prion diseases, including Creutzfeldt-Jakob disease and fatal familial insomnia in humans. Several main topics were discussed, such as the molecular characteristics of prion strains, the cell biology of cellular and pathogenic forms of the prion proteins, the pathogenesis of the diseases they cause, emerging problems, and promising approaches for therapy and new diagnostic tools. The presentations at the Prion 2005 conference provided new insights in both basic and applied research, which will have broad implications for society's needs.
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PMID:Prion 2005: Between Fundamentals and Society's Needs. 1643 84

We established a novel combinatorial method of laser microdissection system and immunoblot analysis in combination with a novel unfolding chaperone (oligomeric Aip2p/Dld2p) that enables us to examine the molecular profile of proteins in the microscopic regions of interest. As a model system for analyzing inclusion bodies associated with various diseases such as Alzheimer's disease, Parkinson's disease, and prion diseases including bovine spongiform encephalopathy (BSE), we applied this novel method to examine brain samples of patients with Pick's disease, a type of progressive presenile dementia with intraneuronal lesions denoted as Pick bodies (PBs) whose major structural components are tau proteins. After boiling in Laemmli's sample buffer according to the established immunoblotting procedures, 500-2000 PBs were initially applied onto SDS-PAGE gels; however, only faint signals were obtained. Remarkably, only one Pick body was sufficient to illustrate an immunoblot signal; this indicates that pretreatment with oligomeric Aip2p/Dld2p enhances the immunoblot sensitivity by more than a 100-fold. This unprecedented property of laser microdissection combined with oligomeric Aip2p/Dld2p may have further potential applications. For example, a number of proteomic strategies for such inclusion bodies depend on liquid chromatography-tandem mass spectrometry (LC-MS/MS); however, sample preparation methods typically involve the use of detergents and chaotropic agents that often interfere with chromatographic separation and/or electrospray ionization. However, the use of oligomeric Aip2p/Dld2p would not interfere with the LC-MS/MS procedures. Therefore, it might significantly facilitate nanoscale analysis, which is often hindered by the aggregation property of the target proteins present under various analytical conditions, particularly, when the sample protein is present in minor quantities.
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PMID:Investigation of laser-microdissected inclusion bodies. 1758 64

Misfolded protein aggregates and inclusion bodies have been associated with various protein conformation disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and prion diseases including bovine spongiform encephalopathy (BSE). Models have been proposed as plausible explanations for the extension and progression of protein aggregates; however, little is known about the initiation process of protein aggregation, particularly in sporadic neurodegenerative diseases. Epidemiological data have suggested a tight association between sporadic neurodegenerative diseases and history of mechanical stresses such as trauma, head injury, and occupational exposures, including professional soccer and boxer's brain that carries histological hallmarks of AD/PD. Here, we propose that mechanical stress is an environmental factor that provokes a disturbance in cellular quality control systems and molecular chaperones that target misfolded proteins. This subsequently initiates protein aggregation and results in sporadic neurodegenerative disorders. Further, continuous and repetitive exposure to environmental mechanical stress, mostly in an unrecognized manner, is inevitable in daily life and thus, it functions as a potential driving force for protein aggregation. In this regard, a recent identification of the fact that an intracellular mechanosensor actually exists may support our notion. Reduction in the mechanical stress in combination with other conventional aspects should facilitate the development of rational therapeutics for these neurodegenerative disorders.
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PMID:Mechanical stress and formation of protein aggregates in neurodegenerative disorders. 1791 Sep 93


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