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)

In the CNS, reactive oxygen species (ROS) have been implicated in a wide range of degenerative processes including amyotrophic lateral sclerosis, ischemia-reperfusion injury, Alzheimer disease, Parkinson disease and aging. However, the exact mechanism is unknown, and there is little information on possible roles of ROS in cell injury and the process on recovery of astrocytes, the most abundant glial cells in the brain. We examined hydrogen peroxide (H2O2)-induced DNA fragmentation and thymidine incorporation into cultured astrocytes as an indicator of the process of recovery from astrocytic DNA injury. Astrocytes were isolated from cerebral cortices of 0-day-old rats and treated with 1 mM dibutyryl cyclic AMP for 4 days. H2O2 of 100 microM stimulated thymidine incorporation into astrocytes. Caffeine, ryanodine, cyclic ADP-ribose (endogenous ryanodine receptor agonist) and beta-NAD+ (precursor of cyclic ADP-ribose) suppressed partially the stimulatory effect of H2O2. Ruthenium red (ryanodine receptor antagonist) facilitated further the stimulatory effect of H2O2. The facilitated effect of ruthenium red on H2O2-induced thymidine incorporation was suppressed by caffeine, ryanodine, cyclic ADP-ribose and beta-NAD+. H2O2-induced DNA fragmentation and astrocytic death were suppressed by ruthenium red. These findings suggest that the process of recovery from astrocytic DNA injury by H2O2 may be regulated by Ca2+ efflux from ryanodine-sensitive intracellular Ca2+ stores.
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PMID:[Role of ryanodine receptors in hydrogen peroxide-induced DNA fragmentation and thymidine incorporation in cultured rat astrocytes]. 1019 Jan 45

Psychosis has been recognized as a common feature in neurodegenerative disease for many years. Hallucinations, delusions, and other psychotic phenomena occur in a wide range of degenerative disorders including Alzheimer disease, Huntington disease, Parkinson's disease, diffuse Lewy body disease, "Parkinson plus" syndromes, Pikc's disease, and other frontotemporal degenerations, amyotrophic lateral sclerosis, and prion associated diseases. It is also interesting that neurodegenerative disease-type dementia may be a feature in some psychotic illnesses such as schizophrenia. Clinical evaluation of psychosis in the setting of dementia presents a significant challenge for clinicians and researchers. Amnesia, language or speech impairments, and behavioral problems amy distort and obscure the presentation of symptoms. However, recognition and understanding of the psychotic manifestations may lead to the institution of more effective therapeutic or preventive options that can serve to delay long term care placement and improve patient and caregiver quality of life. In addition, a more comprehensive understanding of the pathophysiology, neuroanatomical substrates, and distinctive pathological features underlying the development of psychotic symptoms in neurodegenerative diseases may provide important insights into psychotic processes in general.
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PMID:Psychosis in Neurodegenerative Disease. 1032 Apr 31

At present, 8 inherited neurodegenerative disorders (e.g. Huntington disease, Machado-Joseph disease, etc.) are identified to be caused by the polyglutamine-coding CAG triplet expansions in the responsible genes. These disorders commonly demonstrate dominant inheritance, if autosomal, and late onset of their manifestations. Interestingly, the longer expansions result in earlier onset and more severe clinical manifestations. Proteins containing expanded polyglutamine repeats appear to precipitate by self-aggregation, and as a result produce a core disease-related phenotype: neuronal cell death or degeneration. Given that polyglutamine aggregation might be central in neurodegeneration, the parameters that determine the feasibility of the polyglutamines to aggregate would determine the age of onset and the clinical severity. These parameters are postulated to be the concentration and the length of polyglutamines, which is supported by clinical and experimental observations. The stronger neuronal degenerations are always accompanied by the longer polyglutamine stretches and by the higher concentration of the expanded polyglutamines. In other neurodegenerative disorders, such as Alzheimer disease, prion disease, Parkinson disease and amyotrophic lateral sclerosis, precipitation of abnormal proteins is also now considered to play a key role. These observations might lead to the elucidation of universal mechanisms for neurodegeneration and to treatments effective for many neurodegenerative disorders.
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PMID:[Recent progress in the research field on triplet repeat diseases]. 1034 35

Neurotrophic factors are polypeptides primarily known to regulate the survival and differentiation of nerve cells during the development of the peripheral and central nervous systems. The neurotrophic factors act via specific receptors after retrograde axonal transport from the nerve fibre target areas back to the cell bodies, and locally through autocrine and paracrine mechanisms linked to nerve cell activity. In the mature nervous system, neurotrophic factors maintain morphological and neurochemical characteristics of nerve cells and promote activity-dependent dynamic/plastic changes in the synaptic contacts between nerve cells by strengthening functionally active synaptic connections. Induction and increased production of neurotrophic factors in relation to neural injuries are thought to serve protective and reparative purposes. Specific neurotrophic factors have thus been shown to protect nerve cells in a number of experimental models for neurodegenerative diseases, such as Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis, just as specific neurotrophic factors have been shown to stimulate regenerative growth of both peripheral and central nerve fibres. Today, problems with continuous and localized delivery of specific neurotrophins or combinations thereof into the nervous system appear to be the most important obstacle for more widespread clinical application.
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PMID:[Neuronal growth factors--neurotrophins]. 1037 61

Mutations in mitochondrially encoded tRNA genes have been described in a variety of neurological disorders. One such mutation, the A to G transition at nucleotide position 4336 of the mitochondrial tRNA(Gln) gene, has been associated with both Alzheimer and Parkinson disease. We have now performed a complete sequence analysis of all 22 mitochondrially encoded tRNA genes in 20 cases of histologically proven idiopathic Parkinson disease. Genomic DNA extracted from the substantia nigra of frozen or formalin-fixed and paraffin-embedded brains was used for amplification by polymerase chain reaction followed by automated sequencing. Two new homoplasmic point mutations were detected in the genes for tRNA(Thr) (15950 G/A) and tRNA(Pro) (15965 T/C) in 1 patient each. Restriction enzyme digestion revealed absence of the 15950 G/A mutation in 96 controls and in 40 cases of neuropathologically confirmed Alzheimer disease. The 15965 T/C mutation was shown to be absent from 100 control subjects and 47 Alzheimer cases. In addition to the two novel mutations, six known sequence variants were detected in a total of 6 different patients in the genes for tRNA(Asp) (G7521A, 1), tRNA(Arg) (T10463C, 1), tRNA(LeuCUN) (A12308G, 2), and tRNA(Thr) (A15924G, 1; G15928A, 2), including 1 patient carrying the tRNA(Gln) (A4336G) mutation. The G15950A transition affects position 70 of the aminoacyl acceptor stem of tRNA(Thr), which has been implicated as a recognition element for threonyl-tRNA synthetase and, at least in some tRNAs, in the processing of primary mitochondrial transcripts. The T15965C point mutation in the mitochondrial tRNA(Pro) gene alters position 64 of the TpsiC stem. The corresponding nucleotide in bacterial aminoacyl-tRNAs is involved in the interaction with elongation factor Tu. Thus, the two novel mutations are likely to be of functional relevance and could contribute to dopaminergic nerve cell death in affected individuals.
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PMID:Two novel point mutations of mitochondrial tRNA genes in histologically confirmed Parkinson disease. 1036 89

Recently several responsible genes for hereditary neurodegenerative disorders were identified. In some of them the gene products were found to be aggregated. In the case of Alzheimer disease beta protein and apolipoprotein E accumulated in senile plaques. In CAG repeat diseases the polyglutamine aggregates in neuronal nuclei. More recently alpha synuclein accumulates in Lewy bodies in Parkinson disease and tau protein accumulates in NFT of hereditary frontotemporal dementia with tau mutation. Those results suggested that the responsible gene products accumulates in the lesion which the products involve in. However, presenilin which is one of the genes for familial Alzheimer disease accumulates in NFT and on the other hand its mutation changes the production ratio of beta 1-42/40, suggesting that the abnormal gene products not simply accumulate the lesion that it involved. The gene products accumulate in different lesions such as in nuclei of polyglutamine diseases, extracellular plaque and cytoplasm of prion disease and extracellular plaques in Alzheimer disease. Some of them are ubiquitinated and some of them are not. Thus the accumulating process in these disorders seems apparently same but is essentially different. We should study more precisely each pathological process of those disorders.
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PMID:[Neuronal cell death--what we can see and what we cannot]. 1037 83

Aside from physiological tremor, essential tremor (ET) is by far the most common cause of tremor in humans, affecting large numbers of individuals in every human population. The crude prevalence of ET has been conservatively estimated to be between 0.4% and 3.9%, although some estimates of the prevalence of ET among the elderly are higher than 20%. Essential tremor is the most prevalent adult-onset movement disorder, and is also regarded as one of the most common neurological disorders of adults, with a prevalence that is similar to or greater than that of stroke, Alzheimer disease, migraine headache, and lumbosacral pain syndromes. Essential tremor is as much as 20 times more prevalent than Parkinson disease.
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PMID:A new twist for stopping the shakes? Revisiting GABAergic therapy for essential tremor. 1040 81

Neurodegenerative diseases are highly devastating disorders characterized by the damage and loss of discrete neuronal populations. Until recently, it was assumed that the ability of the central nervous system to recover from injury was extremely limited. However, many "in vitro" and "in vivo" studies have shown that neurotrophic factor are able to prevent or inhibit neuronal cell death induced by a variety of insults. Accordingly, trophic factors may represent a new tool for treating neuronal injury and death in a variety of neurodegenerative diseases. In his review, the therapeutic possibilities of neurotrophins in the treatment of Parkinson's disease, Alzheimer disease and amyotrophic lateral sclerosis are analysed.
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PMID:[Neurotrophins. II: therapeutic potential]. 1042 Sep 24

Recent reports have established oxidative stress and damage as playing a role in the pathogenesis of a number of neurodegenerative diseases including Alzheimer disease, Parkinson disease, corticobasal degeneration, Pick's disease and Alexander's disease. Here we present evidence that oxidative damage is also one of the earliest cytopathological markers of neuronal dysfunction in frontotemporal dementia.
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PMID:Role of oxidative stress in frontotemporal dementia. 1043 48

A growing body of evidence suggests that the non-Abeta component of Alzheimer's disease amyloid precursor protein (NACP) or alpha-synuclein contributes to the neurodegenerative processes in Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In the present study antisera to the N terminus and the NAC domain of the alpha-synuclein protein were employed to elucidate the expression pattern in brains of patients with AD, PD, DLB and control specimen. Alpha-synuclein exhibited an overall punctuate expression profile compatible with a synaptic function. Interestingly, while Lewy bodies were strongly immunoreactive, none of the alpha-synuclein antisera revealed staining in mature beta-amyloid plaques in AD. These observations suggest that alpha-synuclein does not contribute to late neurodegenerative processes in AD brains.
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PMID:Alpha-synuclein accumulates in Lewy bodies in Parkinson's disease and dementia with Lewy bodies but not in Alzheimer's disease beta-amyloid plaque cores. 1046 11


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