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)

The possibility of a pathway, common to progression, in entities in which activated macrophages or microglia are present, amenable to particular therapies, is discussed. Immunoglobulin synthesis and activation of the complement pathway may be critical elements in progression. It is possible progression in a proportion of patients may be lessened by immunomodulatory and immunosuppressive therapies in "combination", immunomodulatory therapies inhibiting the antigen presenting cell, and immunosuppressive therapies lymphocyte immunoglobulin synthesis. Such "combination therapy" may inhibit more effectively immunoglobulin synthesis and complement pathway activation, thus "downregulating" activated microglia or macrophages. In this perspective, the disease phenotype reflects the particular cell or tissue targeted by activated microglia or macrophages, a form of "auto-immunity", devoid of the usual inflammatory markers. Amplification of immunoglobulin synthesis by the complement pathway, particularly the component, C3d, leads to progression of the process. Diseases in which such "combination" therapy might lessen the rate of decline include Alzheimer's disease, Parkinson's disease, multiple sclerosis, macular degeneration, and diabetes.
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PMID:Progression of disease and a remedy: causative role of macrophages and microglia: remedial effect of immunomodulatory and immunosuppressive therapies "in combination". 1682 80

The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the United States. It consists of 15,924 white male twin pairs born in the years 1917 to 1927 (inclusive), both of whom served in the armed forces, mostly during World War II. This article updates activity in this registry since the earlier 2002 article in Twin Research. The results of clinically based studies on dementia, Parkinson's disease, age-related macular degeneration, and primary osteoarthritis were published, as well as articles based on previously collected questionnaire data on chronic fatigue syndrome, functional limitations, and healthy aging. In addition, risk factor studies are being planned to merge clinical data with earlier collected risk factor data from questionnaires. Examination data from the subset of National Heart, Lung, and Blood Institute (NHLBI) twins resulted in a number of articles, including the relationship of endogenous sex hormones to coronary heart disease and morphological changes in aging brain structures. The NEO Five-Factor Personality Inventory (a paper-and-pencil self-administered questionnaire) has been fielded for the first time. A push to consolidate the various data holdings of the registry is being made.
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PMID:Update on the NAS-NRC Twin Registry. 1725 41

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.
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PMID:Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene. 1741

Complement can damage host tissue when overactivated. Evidence of complement self damage exists for Alzheimer disease (AD), age-related macular degeneration, type 1 diabetes mellitus (T1DM), and Parkinson disease (PD). Known complement activators include Abeta, found in AD, and IgG found in T1DM. We compared their complement activating ability in vitro with those of islet amyloid polypeptide (IAPP), which aggregates in the pancreas of T2DM, and alpha-synuclein (alpha-Syn), which aggregates in PD. We found that IAPP and the alternatively spliced alpha-Syn 112 form, but not full-length alpha-Syn 140, activated complement in vitro. Complement activation may contribute to death of insulin-secreting cells in T2DM or to neuronal death in Parkinson disease (PD) and related synucleinopathies where alpha-Syn 112 occurs. This suggests the possibility of anti-inflammatory treatment in these pathologies. It also suggests that blockers of complement activation may be an appropriate therapeutic target for a range of age-related degenerative diseases.
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PMID:Complement activation by islet amyloid polypeptide (IAPP) and alpha-synuclein 112. 1745 37

Foods contain many bioactive compounds that can improve humans' health, helping to decrease the risk of cataract, macular degeneration, cardiovascular and neurological diseases, osteoporosis, and cancer. Regular practice of exercise and physical activity could also help to drive away aging-associated diseases (obesity, osteoporosis, type 2 diabetes, hypertension, Alzheimer's disease, Parkinson's disease, dementia, and stroke). Exercise recommendations to promote both women's and men's health and disease conditions that hinder exercise practice are described. Health promotion practices should focus on both dietary intake of functional foods and regular practice of exercise within the framework of a healthy lifestyle.
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PMID:Functional foods and physical activities in health promotion of aging people. 1798 Sep 78

Oxidative stress occurs when the level of prooxidants exceeds the level of antioxidants in cells resulting in oxidation of cellular components and consequent loss of cellular function. Oxidative stress is implicated in wide range of age-related disorders including Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis (ALS), Huntington's disease and the aging process itself. In the anterior segment of the eye, oxidative stress has been linked to lens cataract and glaucoma while in the posterior segment of the eye oxidative stress has been associated with macular degeneration. Key to many oxidative stress conditions are alterations in the efficiency of mitochondrial respiration resulting in superoxide (O(2)(-)) production. Superoxide production precedes subsequent reactions that form potentially more dangerous reactive oxygen species (ROS) species such as the hydroxyl radical (OH), hydrogen peroxide (H(2)O(2)) and peroxynitrite (OONO(-)). The major source of ROS in the mitochondria, and in the cell overall, is leakage of electrons from complexes I and III of the electron transport chain. It is estimated that 0.2-2% of oxygen taken up by cells is converted to ROS, through mitochondrial superoxide generation, by the mitochondria. Generation of superoxide at complexes I and III has been shown to occur at both the matrix side of the inner mitochondrial membrane and the cytosolic side of the membrane. While exogenous sources of ROS such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins may contribute to the oxidative milieu, mitochondria are perhaps the most significant contribution to ROS production affecting the aging process. In addition to producing ROS, mitochondria are also a target for ROS which in turn reduces mitochondrial efficiency and leads to the generation of more ROS in a vicious self-destructive cycle. Consequently, the mitochondria have evolved a number of antioxidant and key repair systems to limit the damaging potential of free oxygen radicals and to repair damaged proteins (Fig. 1). The aging eye appears to be at considerable risk from oxidative stress. This review will outline the potential role of mitochondrial function and redox balance in age-related eye diseases, and detail how the methionine sulfoxide reductase (Msr) protein repair system and other redox systems play key roles in the function and maintenance of the aging eye.
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PMID:Mitochondrial function and redox control in the aging eye: role of MsrA and other repair systems in cataract and macular degenerations. 1858 75

Sildenafil, a phosphodiesterase-5 inhibitor commonly used for erectile dysfunction, may also have a beneficial therapeutic effect in the treatment of stroke, subarachnoid hemorrhage, dementia, learning, and neurodegenerative disorders by enhancing angiogenesis and neurogenesis. It also favorably influences the nitric oxide-cyclic guanosine monophosphate pathways, which are involved in the pathogenesis of a number of neurological diseases. Its potential therapeutic role in the treatment of the neurological disorders mentioned above is still under preclinical investigation. Sildenafil is currently being used to treat erectile dysfunction in patients with multiple sclerosis, Parkinson disease, multisystem atrophy, and spinal cord injury by improving their neurologically related erectile dysfunction. Conversely, it has been implicated in a number of neurological problems, such as intracerebral hemorrhage, migraine, seizure, transient global amnesia, nonarteritic anterior ischemic optic neuropathy, macular degeneration, branch retinal artery occlusion, and ocular muscle palsies. Thus, preclinical and very limited clinical data suggest that sildenafil may have therapeutic potential in selected neurological disorders. However, numerous reports are available regarding neurological adverse events ascribed to the drug. Although sildenafil shows some promise as a therapeutic agent in selected neurological disorders, well-designed clinical trials are needed before the agent can be recommended for use in any neurological disorder.
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PMID:Role of sildenafil in neurological disorders. 1905 Apr 13

Oxysterols resulting from spontaneous or enzymatic oxidation of cholesterol are present in numerous foodstuffs and have been identified at increased levels in the plasma and the vascular walls of patients with cardiovascular diseases, especially in atherosclerotic lesions. Consequently, their role in lipid disorders is widely suspected, but they may also contribute to the development of important degenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, osteoporosis, age-related macular degeneration, and cataract. Since these pathologies can be associated with the presence of apoptotic cells, oxidative and inflammatory processes, and lipid disorders, the ability of oxysterols to trigger cell death, activate oxidation and inflammation, and modulate lipid homeostasis is being extensively studied. There are several important considerations regarding the physiological/pathophysiological functions and activities of the different oxysterols. It is therefore important to determine their biological activities and identify their signaling pathways, when they are used either in isolation or as mixtures. In these conditions, oxysterols may have cytotoxic, oxidative, and/or inflammatory effects, or no effects whatsoever. Moreover, with cytotoxic oxysterols, a substantial accumulation of polar lipids in cytoplasmic multilamellar structures was observed, demonstrating that cytotoxic oxysterols were phospholipidosis inducers. This basic knowledge on oxysterols contributes to a better understanding of the associated pathologies, so that new treatments and drugs can be designed.
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PMID:Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis. 1924 5

The detection of epistatic interactive effects of multiple genetic variants on the susceptibility of human complex diseases is a great challenge in genome-wide association studies (GWAS). Although methods have been proposed to identify such interactions, the lack of an explicit definition of epistatic effects, together with computational difficulties, makes the development of new methods indispensable. In this paper, we introduce epistatic modules to describe epistatic interactive effects of multiple loci on diseases. On the basis of this notion, we put forward a Bayesian marker partition model to explain observed case-control data, and we develop a Gibbs sampling strategy to facilitate the detection of epistatic modules. Comparisons of the proposed approach with three existing methods on seven simulated disease models demonstrate the superior performance of our approach. When applied to a genome-wide case-control data set for Age-related Macular Degeneration (AMD), the proposed approach successfully identifies two known susceptible loci and suggests that a combination of two other loci -- one in the gene SGCD and the other in SCAPER -- is associated with the disease. Further functional analysis supports the speculation that the interaction of these two genetic variants may be responsible for the susceptibility of AMD. When applied to a genome-wide case-control data set for Parkinson's disease, the proposed method identifies seven suspicious loci that may contribute independently to the disease.
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PMID:Epistatic module detection for case-control studies: a Bayesian model with a Gibbs sampling strategy. 1941 24

Transplantation of pigment epithelial cells in patients with age-related macular degeneration and Parkinson's disease has the potential to improve functional rehabilitation. Genetic modification of cells before transplantation may allow the delivery of neuroprotective factors to achieve functional improvement. As transplantation of cells modified using viral vectors is complicated by the possible dissemination of viral particles and severe immune reactions, we have explored non-viral methods to insert genetic material in pigment epithelial cells. Using lipofection or nucleofection ARPE-19 cells, freshly isolated and primary retinal and iris pigment epithelial (IPE) cells were transfected with plasmids encoding green fluorescent protein (GFP) and with three plasmids encoding recombinant pigment epithelium-derived factor (PEDF) and GFP. Transfection efficiency was evaluated by fluorescence microscopy and stability of protein expression by immunoblotting. Pigment epithelial cells were successfully transfected with plasmid encoding GFP. Expression of GFP in ARPE-19 was transient, but was observed for up to 1 year in IPE cells. Analysis of pigment epithelial cells transfected with PEDF plasmids revealed that PEDF fusion proteins were successfully expressed and functionally active. In conclusion, efficient transfer of genetic information in pigment epithelial cells can be achieved using non-viral transfection protocols.
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PMID:High efficiency non-viral transfection of retinal and iris pigment epithelial cells with pigment epithelium-derived factor. 1974 32


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