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)

A consistent constellation of clinical signs and symptoms define the Rett syndrome, the most prominent of which are disorders of movement and tone. Preliminary pathologic and neurochemical data indicate predominant involvement of the nigrostriatal dopaminergic pathways and the cholinergic system of the basal forebrain region. The age of onset differentiates the Rett syndrome from Alzheimer and Parkinson disease with similar lesions. PET scanning makes it possible to relate the chemistry of the brain to function by measuring the number and affinity of neuroreceptors, metabolism in specific brain regions, and provide important determinants of the underlying mechanisms in disease states.
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PMID:Positron emission tomography in the Rett syndrome: clinical, biochemical and pathological correlates. 138 77

A role of neurotrophic factors has been postulated in some human neurodegenerative disorders such as Alzheimer's and Parkinson's disease. The known developmental effects of these substances suggested that, in some neurologic diseases affecting children, neurotrophic factors might be inadequate. Using a sensitive, two-site enzyme-linked immunoassay, we examined the content of nerve growth factor in the cerebrospinal fluid of 11 children with Rett syndrome and of 24 control patients with various neurologic diagnoses or suffering from other diseases. Nerve growth factor levels were significantly lower in the cerebrospinal fluid of the patients with Rett syndrome than in control patients. The lower level of cerebrospinal fluid nerve growth factor in Rett syndrome suggests that lack of nerve growth may be involved in the pathogenesis of this disease or reflect the underlying brain damage present.
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PMID:Low levels of nerve growth factor in cerebrospinal fluid of children with Rett syndrome. 880 19

Feeding abilities in 20 individuals with Rett syndrome aged 1 1/2 to 33 years were investigated by history and clinical assessment during a meal, followed by videofluoroscopy of feeding. All were shown to have reduced movements of the mid and posterior tongue, with premature spillover of food and liquid from the mouth into the pharynx. They also showed delayed pharyngeal swallow, but otherwise pharyngeal problems were minimal. These findings were noted to be similar to those in Parkinson's disease. Those individuals with the most general neurological impairment tended to have the worst feeding problems and were smaller and malnourished.
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PMID:Feeding ability in Rett syndrome. 923

In patients with Rett syndrome (RS), a peculiar type of disturbance in phasic chin muscle activity during rapid-eye-movement sleep (REMS) (e.g. an elevation of phasic inhibition index (PII) without an affection of tonic inhibition index (TII)) has been reported. The similar disturbance in REMS was reported not only in child patients with infantile spasms, severe myoclonic epilepsy in infancy (SMEI), severe nocturnal enuresis, and autism but also in adult patients with Parkinson's disease (PD). Except for SMEI and PD, patients with the other four clinical entities including RS could express autistic tendency. Since the responsible lesion for the occurrence of an elevation of PII with a normal TII value is likely to be in the pontine tegmentum, this subcortical structure is hypothesized to be involved in the appearance of autistic tendency.
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PMID:Disturbance of phasic chin muscle activity during rapid-eye-movement sleep. 1173 53

The author reviews the applications of transcranial magnetic stimulation (TMS) in a series of movement disorders--namely, Parkinson's disease, corticobasal degeneration, multiple system atrophy, progressive supranuclear palsy, essential tremor, dystonia, Huntington's chorea, myoclonus, the ataxias, Tourette's syndrome, restless legs syndrome, Wilson's disease, Rett syndrome, and stiff-person syndrome. Single- and paired-pulse TMS studies have been done mainly for pathophysiologic purposes. Repetitive TMS has been used largely for therapy. Many TMS abnormalities are seen in the different diseases. They concur to show that motor cortical areas and their projections are the main target of the basal ganglia dysfunction typical of movement disorders. Interpretation has not always been clear, and sometimes there were discrepancies and contradictions. Largely, this may be the result of the extreme heterogeneity of the methods used and of the patients studied. It is premature to give repetitive TMS a role in treatment. Overall, however, TMS gives rise to a new, outstanding enthusiasm in the neurophysiology of movement disorders. There is reason to predict that TMS, with its continuous technical refinement, will prove even more helpful in the near future. Then, research achievements are reasonably expected to spill over into clinical practice.
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PMID:Applications of transcranial magnetic stimulation in movement disorders. 1243 85

Epigenetic chromatin remodeling and modifications of DNA represent central mechanisms for regulation of gene expression during brain development and in memory formation. Emerging evidence implicates epigenetic modifications in disorders of synaptic plasticity and cognition. This review focuses on recent findings that HDAC inhibitors can ameliorate deficits in synaptic plasticity, cognition, and stress-related behaviors in a wide range of neurologic and psychiatric disorders including Huntington's disease, Parkinson's disease, anxiety and mood disorders, Rubinstein-Taybi syndrome, and Rett syndrome. These agents may prove useful in the clinic for the treatment of the cognitive impairments that are central elements of many neurodevelopmental, neurological, and psychiatric disorders.
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PMID:Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. 1820 23

RNA is not a simple intermediate between DNA and proteins. RNA is widely transcribed from a variety of genomic regions, and researchers are extensively exploring the functional roles and the regulations of non-coding RNAs and small RNAs including siRNAs and mRNAs. In addition, the human genome project disclosed that we humans carry as few as approximately 22,000 genes. Humans employ tissue-specific and developmental stage-specific alternative splicing to generate a large variety of proteins in a specific cell at a specific developmental stage. Neurological disorders are not the exceptions that can escape from aberrations of the splicing machinery. A large variety of neurological disorders is causally associated with RNA pathologies, but this lecture was mostly focused on aberrant splicings due to pathological alterations of splicing cis- and trans-elements. The neurological diseases covered include congenital myasthenic syndromes, genetic forms of Parkinson's disease, spastic paraplegia, myotonic dystrophy types 1 and 2, sporadic Alzheimer's disease, facioscapulohumeral dystrophy, fragile X-associated tremor/ ataxia syndrome, Rett syndrome, Prader-Willi syndrome, spinocerebellar atrophy type 8, and Waardenburg-Shah syndrome. Potential therapeutic modalities targeting RNA are addressed on congenital myasthenic syndromes, Duchenne muscular dystrophy, spinal muscular atrophy, and familial dysautonomia.
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PMID:[RNA pathologies in neurological disorders]. 1821 Aug 2

The approval of suberoylanilide hydroxamic acid by the FDA for the treatment of cutaneous T-cell lymphoma in October, 2006 sparked a dramatic increase in the development of inhibitors for the class of enzymes known as the histone deacetylases (HDACs). In recent years, a large number of combination therapies involving histone deacetylase inhibitors (HDACIs) have been developed for the treatment of a variety of malignancies and neurodegenerative disorders. Promising evidence has been reported for the treatment of pancreatic cancer, prostate cancer, and leukemia as well as a number of other previously difficult to treat cancers. Drug combination approaches have also shown promise for the treatment of mood disorders including bipolar disorder and depression. In addition to these drug combination approaches, HDACIs alone have demonstrated effectiveness in the treatment of Parkinson's disease, Alzheimer's disease, Rubinstein-Taybi syndrome, Rett syndrome, Friedreich's ataxia, Huntington's disease, multiple sclerosis, anxiety, and schizophrenia. Adverse inflammatory affects observed with traumatic brain injury and arthritis have also been alleviated by treatment with certain HDACIs. Based on the diverse utility and wide range of mechanistic actions observed with this class of drugs, the future development of better drug combination therapies and more selective HDACIs is warranted.
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PMID:Creating zinc monkey wrenches in the treatment of epigenetic disorders. 1954 31

Epigenetic mechanisms such as DNA methylation and modifications to histone proteins regulate high-order DNA structure and gene expression. Aberrant epigenetic mechanisms are involved in the development of many diseases, including cancer. The neurological disorder most intensely studied with regard to epigenetic changes is Rett syndrome; patients with Rett syndrome have neurodevelopmental defects associated with mutations in MeCP2, which encodes the methyl CpG binding protein 2, that binds to methylated DNA. Other mental retardation disorders are also linked to the disruption of genes involved in epigenetic mechanisms; such disorders include alpha thalassaemia/mental retardation X-linked syndrome, Rubinstein-Taybi syndrome, and Coffin-Lowry syndrome. Moreover, aberrant DNA methylation and histone modification profiles of discrete DNA sequences, and those at a genome-wide level, have just begun to be described for neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, and in other neurological disorders such as multiple sclerosis, epilepsy, and amyotrophic lateral sclerosis. In this Review, we describe epigenetic changes present in neurological diseases and discuss the therapeutic potential of epigenetic drugs, such as histone deacetylase inhibitors.
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PMID:Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. 1983 91

Adenosine A(2A) receptors (A(2A)Rs) appear to play important roles in inflammation and in certain diseases of the nervous system. Pharmacological modulation of A(2A)Rs is particularly useful in Parkinson's disease and has been tested in schizophrenia. However, little is known about the regulation of A(2A)R gene (ADORA2A). A bioinformatic analysis revealed the presence of three CpG islands in the 5' UTR region of human ADORA2A. Next, HeLa, SH-SY5Y and U87-MG cells were treated for 48 h with 5 muM 5-azacytidine (Aza). Increased A(2A)R levels were demonstrated in HeLa and SH-SY5Y cells when compared with non-treated cells. No modifications were seen in U87-MG cells. The increased A(2A)R mRNA and protein levels were accompanied by a loss of DNA methylation pattern in HeLa and SH-SY5Y cells, as measured with the SEQUENOM MassArray platform. The Aza treatment also reduced the affinity of a methyl-CpG-binding protein for ADORA2A by quantitative chromatin immunoprecipitation in HeLa cells. Interestingly, A(2A)R levels were reduced by S-adenosyl-l-methionine treatment in U87-MG and methyl-CpG-binding protein affinity was increased for ADORA2A by quantitative chromatin immunoprecipitation. Therefore, these results show for the first time that DNA methylation plays a role in ADORA2A transcription and, subsequently, in constitutive A(2A)R cell surface levels.
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PMID:DNA methylation regulates adenosine A(2A) receptor cell surface expression levels. 2000 25


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