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)

Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that reduces superoxide anion to hydrogen peroxide in cell mitochondria. MnSOD is overexpressed in normal aging brain and in various central nervous system disorders; however, the mechanisms mediating the upregulation of MnSOD under these conditions remain poorly understood. We previously reported that cysteamine (CSH) and other pro-oxidants rapidly induce the heme oxygenase-1 (HO-1) gene in cultured rat astroglia followed by late upregulation of MnSOD in these cells. In the present study, we demonstrate that antecedent upregulation of HO-1 is necessary and sufficient for subsequent induction of the MnSOD gene in neonatal rat astroglia challenged with CSH or dopamine, and in astroglial cultures transiently transfected with full-length human HO-1 cDNA. Treatment with potent antioxidants attenuates MnSOD expression in HO-1-transfected astroglia, strongly suggesting that intracellular oxidative stress signals MnSOD gene induction in these cells. Activation of this HO-1-MnSOD axis may play an important role in the pathogenesis of Alzheimer disease, Parkinson disease and other free radical-related neurodegenerative disorders. In these conditions, compensatory upregulation of MnSOD may protect mitochondria from oxidative damage accruing from heme-derived free iron and carbon monoxide liberated by the activity of HO-1.
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PMID:Role of heme oxygenase-1 in the regulation of manganese superoxide dismutase gene expression in oxidatively-challenged astroglia. 1094 21

Occupational exposure to electromagnetic fields has been associated with neurological diseases such as amyotrophic lateral sclerosis, senile dementia, Parkinson disease, and Alzheimer disease. I studied the incidence of central nervous system diseases in 30,631 persons employed in Danish utility companies between 1900 and 1993. I linked the cohort to the nationwide, population-based Danish National Register of Patients and compared the numbers of cases of these diseases observed between 1978 and 1993 with the corresponding rates in the general population. In addition I fit to the data on utility workers a multiplicative Poisson regression model in relation to estimated levels of exposure to 50-Hz electromagnetic fields. Overall, there was an increase in risk for senile dementia and motor neuron diseases combined. The incidences of Parkinson disease, Alzheimer disease, and other diseases of the central nervous system were essentially unrelated to exposure to electromagnetic fields. A decreased risk of epilepsy compared with the general population probably reflects a healthy worker effect; I observed an increased risk of epilepsy based on internal comparisons. The increased risk for senile dementia and motorneuron diseases may be associated with above-average levels of exposure to electromagnetic fields.
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PMID:Exposure to electromagnetic fields and risk of central nervous system disease in utility workers. 1095 6

Neurosin, a novel type of trypsin-like serine protease, has been shown to be preferentially expressed in human brain by northern blotting. We examined neurosin immunolabeling in the brains of neurologically normal persons and patients with Alzheimer's disease (AD) and with Parkinson's disease. We also identified the expression of the mRNA for neurosin by in situ hybridization histochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The neurosin antibody stained all of the nuclei of various cell types. In neurons, there was also staining of neuronal cytoplasm, nucleoli and their processes. In AD, staining of neurons with processes was rare in the damaged areas. Some senile plaques, extracellular tangles and Lewy bodies were also positive for neurosin. Expression of the mRNA for neurosin was seen in neurons in the gray matter, and in microglial cells in the white matter. In AD, the intensity of the signal for neurosin mRNA in the gray matter was decreased compared with normal control brains. The relative levels of neurosin mRNA in AD brains, measured by RT-PCR, were lower than those in controls. These results suggest that in human brain neurosin plays various physiological roles, and that in AD this molecule, like other serine proteases, may have a role in the degradation of such substances as beta-amyloid protein.
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PMID:Localization of a novel type trypsin-like serine protease, neurosin, in brain tissues of Alzheimer's disease and Parkinson's disease. 1099 58

Neurodegenerative and dementing disorders such as Parkinson disease and Alzheimer disease are among the most common diseases of advanced age. Despite progress in the clinical diagnosis of neurodegenerative disorders, definite diagnosis for most of these disorders is still possible only by neuropathological examination of the brain. The neuropathological diagnosis and classification of neurodegenerative disorders has made clear advances in recent years, particularly due to the results of genetic and biochemical studies, resulting in the development of new disease-specific antibodies. Internationally recognized consensus criteria for most neurodegenerative disorders allow a definite and standardized diagnosis to be made. To obtain further knowledge about the etiopathogenesis, particularly with regard to new therapeutic strategies, studies with clinically and neuropathologically well-documented cases are needed. The project "Brain-Net" has therefore been established with the aim of setting up a German Brain and Tissue Bank for Diseases of the Central Nervous System. The project is funded by the Federal Ministry of Education and Research.
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PMID:[Neuropathological diagnosis of neurodegenerative and dementia diseases]. 1109 9

Current knowledge of sporadic degenerative disorders suggests that, despite their multifactorial etiopathogenesis, genetics plays a primary role in orchestrating the pathological events, and even dramatically changes the disease phenotype from patient to patient. Genes may act as susceptibility factors, increasing the risk of disease development, or may operate as regulatory factors, modulating the magnitude and severity of pathogenic processes or the response to drug treatment. The goal of pharmacogenomics is the application of this knowledge to elaborate more specific and effective treatments and to tailor therapies to individual patients according to their genetic profile. Here, we outline the leading theories on the etiopathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer disease, and we review the potential role of genetic variations, such as gene mutations and polymorphisms, in each context. We also suggest potential targets for new therapeutic approaches and variability factors for current treatments based on genotype features. Finally, we propose a few options of preventive therapeutic interventions in patients with a high genetic risk of disease.
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PMID:Pharmacogenomics of neurodegenerative diseases. 1117 59

Degeneration and death of neurons is the fundamental process responsible for the clinical manifestations of many different neurological disorders of aging, incuding Alzheimer's disease, Parkinson's disease and stroke. The death of neurons in such disorders involves apoptotic biochemical cascades involving upstream effectors (Par-4, p53 and pro-apoptotic Bcl-2 family members), mitochondrial alterations and caspase activation. Both genetic and environmental factors, and the aging process itself, contribute to intiation of such neuronal apoptosis. For example, mutations in the amyloid precursor protein and presenilin genes can cause Alzheimer's disease, while head injury is a risk factor for both Alzheimer's and Parkinson's diseases. At the cellular level, neuronal apoptosis in neurodegenerative disorders may be triggered by oxidative stress, metabolic compromise and disruption of calcium homeostasis. Neuroprotective (antiapoptotic) signaling pathways involving neurotrophic factors, cytokines and "conditioning responses" can counteract the effects of aging and genetic predisposition in experimental models of neurodegenerative disorders. A better understanding of the molecular underpinnings of neuronal death is leading directly to novel preventative and therapeutic approaches to neurodegenerative disorders.
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PMID:Neurodegenerative disorders and ischemic brain diseases. 1132 Oct 43

Music therapy is a science that has been applied since many centuries ago, but it has been organized as a profession during the past century. This science studies the therapeutic effects of music in human beings. Professionals who practice this science are called "music therapists" and they must be trained not only in music theory and performance, but also in psychology, anatomy, research techniques, and other subjects. Today, we can find music therapy research in many areas such as the effects of music in children with autism, adults with psychiatric illnesses, elderly with Alzheimer and Parkinson disease, people with brain injuries, among others. Numerous studies demonstrate the functionality of music therapy in patients with neurological disorders. These studies show that music helps patients to gain control over their walking patterns after a brain injury, stimulates long and short term memory in patients with Alzheimer disease, and increase self esteem and social interaction in elders.
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PMID:[Application of music therapy in medicine]. 1135 76

The term alpha-synucleinopathy is used to name a group of disorders having in common the abnormal deposition of alpha-synuclein in the cytoplasm of neurons or glial cells, as well as in extracellular deposits of amyloid. In Parkinson's disease and Lewy body dementia, alpha-synuclein is the main component of Lewy bodies and dystrophic neurites; alpha-synuclein also accumulates in the cytoplasm of glial cells. In multiple system atrophy, alpha-synuclein conforms the cytoplasmic oligodendroglial inclusions and the neuronal inclusions which are the hallmark of this disease. Finally, the amyloidogenic fragment 61-95 amino acids of alpha-synuclein is the non-Abeta component of senile plaque amyloid in Alzheimer disease. Accumulations of alpha-synuclein in all these disorders have in common a fibrilar configuration, but they differ in the binding of alpha-synuclein to distinct proteins with the exception of ubiquitin whose binding to alpha-synuclein is common to all alpha-synuclein inclusions. The mechanisms leading to alpha-synuclein fragmentation and aggegation into extracellular amyloid are not known, although alpha-synuclein fragment and betaA4 aggregates are the result of abnormal cleavage of large precursors. On the other hand, several studies have shown that alpha-synuclein may adopt a fibrilar conformation and give rise to insoluble forms and high molecular weight aggregates in vitro. Similar complexes have also been observed in alpha-synucleinopathies. Although studies in vitro and in vivo have shown toxic effects of alpha-synuclein, the consequence of alpha-synuclein deposition on cell survival in alpha-synucleinopathies is not known.
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PMID:[Alpha-synucleinopathies]. 1141 9

Hallervorden-Spatz syndrome (HSS) is an autosomal recessive neurodegenerative disorder associated with iron accumulation in the brain. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals iron deposits in the basal ganglia. In this respect, HSS may serve as a model for complex neurodegenerative diseases, such as Parkinson disease, Alzheimer disease, Huntington disease and human immunodeficiency virus (HIV) encephalopathy, in which pathologic accumulation of iron in the brain is also observed. Thus, understanding the biochemical defect in HSS may provide key insights into the regulation of iron metabolism and its perturbation in this and other neurodegenerative diseases. Here we show that HSS is caused by a defect in a novel pantothenate kinase gene and propose a mechanism for oxidative stress in the pathophysiology of the disease.
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PMID:A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. 1147 80

Transgenic Drosophila melanogaster and Caenorhabditis elegans strains have been engineered to express human proteins associated with neurodegenerative diseases. These model systems include transgenic animals expressing beta-amyloid peptide (Alzheimer's disease), polyglutamine repeat proteins (Huntington's disease, Spinocerebellar ataxia), and alpha-synuclein (Parkinson's disease). In most of these invertebrate models, some aspects of the human diseases are reproduced. Although expression of all these proteins in transgenic mice has been instructive, the invertebrate models offer experimental advantages (e.g. forward genetic screens) that can potentially address some of the outstanding questions regarding the cellular processes underlying these diseases. This review considers what has been learned from these invertebrate models, and speculates what further insight may be gained from them.
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PMID:Transgenic invertebrate models of age-associated neurodegenerative diseases. 1151 1


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