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)

Endosulfine-alpha (ENSA) is a 121-residue cAMP-regulated phosphoprotein, originally identified as an endogenous regulator of ATP-sensitive potassium channels. ENSA has been implicated in the regulation of insulin secretion, and expression of ENSA is decreased in brains of both Alzheimer's disease (AD) and Down's syndrome patients. We recently described membrane-dependent interactions between ENSA and the Parkinson's disease associated protein alpha-synuclein. Here we characterize the conformational change in ENSA that occurs upon binding to membranes. Secondary chemical shift analysis demonstrates formation of four helices in the lipid-bound state that are not present in the absence of lipid. The helical structure is maintained in several different lipid mimetics (sodium dodecyl sulfate, dodecyl phosphocholine, lyso 1-palmitoyl phosphatidylglycerol, and phospholipid vesicles). Introduction of a mutation (S109E) to mimic PKA phosphorylation of ENSA leads to a perturbation of the fourth helix and disrupts the interaction with alpha-synuclein. These data establish ENSA as an intrinsically unstructured protein that adopts a stable structure upon membrane binding, properties it shares with its binding partner alpha-synuclein.
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PMID:Membrane-induced folding of the cAMP-regulated phosphoprotein endosulfine-alpha. 1897 46

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common causes of dementia and movement disorders in the elderly. While progressive accumulation of oligomeric amyloid-beta protein (Abeta) has been identified as one of the central toxic events in AD leading to synaptic dysfunction, accumulation of alpha-synuclein (alpha-syn) resulting in the formation of oligomers has been linked to PD. Most of the studies in AD have been focused on investigating the role of Abeta and Tau; however, recent studies suggest that alpha-syn might also play a role in the pathogenesis of AD. For example, fragments of alpha-syn can associate with amyloid plaques and Abeta promotes the aggregation of alpha-syn in vivo and worsens the deficits in alpha-syn tg mice. Moreover, alpha-syn has also been shown to accumulate in limbic regions in AD, Down's syndrome, and familial AD cases. Abeta and alpha-syn might directly interact under pathological conditions leading to the formation of toxic oligomers and nanopores that increase intracellular calcium. The interactions between Abeta and alpha-syn might also result in oxidative stress, lysosomal leakage, and mitochondrial dysfunction. Thus, better understanding the steps involved in the process of Abeta and alpha-syn aggregation is important in order to develop intervention strategies that might prevent or reverse the accumulation of toxic proteins in AD.
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PMID:Role of synucleins in Alzheimer's disease. 1955 56

Sequence tag analysis using serial analysis of gene expression (SAGE) is a powerful strategy for the quantitative analysis of gene expression in human genetic disorders. SAGE facilitates the measurement of mRNA transcripts and generates a non-biased gene expression profile of normal and pathological disease tissue. In addition, the SAGE technique has the capacity of detecting the expression of novel transcripts allowing for the identification of previously uncharacterised genes, thus providing a unique advantage over the traditional microarray-based approach for expression profiling. The technique has been successful in providing pathological gene expression profiles in a number of common genetic disorders including diabetes, cardiovascular disease, Parkinson disease and Down syndrome. When combined with next generation sequencing platforms, SAGE has the potential to become a more powerful and sensitive technique making it more amenable for diagnostic use. This review will therefore discuss the application of SAGE to several common genetic disorders and will further evaluate its potential use in diagnosing human genetic disease.
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PMID:Application of serial analysis of gene expression to the study of human genetic disease. 1959 Aug 94

G protein-gated inwardly rectifying potassium (GIRK) channels hyperpolarize neurons in response to activation of many different G protein-coupled receptors and thus control the excitability of neurons through GIRK-mediated self-inhibition, slow synaptic potentials and volume transmission. GIRK channel function and trafficking are highly dependent on the channel subunit composition. Pharmacological investigations of GIRK channels and studies in animal models suggest that GIRK activity has an important role in physiological responses, including pain perception and memory modulation. Moreover, abnormal GIRK function has been implicated in altering neuronal excitability and cell death, which may be important in the pathophysiology of diseases such as epilepsy, Down's syndrome, Parkinson's disease and drug addiction. GIRK channels may therefore prove to be a valuable new therapeutic target.
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PMID:Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. 2038 5

This short review describes a series of case-control studies on the concentration and oxidative activity of ceruloplasmin (CP) in serum and the activity of superoxide dismutase (SOD1) in erythrocytes in patients with Alzheimer's disease (AD), Parkinson's disease (PD) and Down's syndrome (DS). The same parameters were re-examined in the PD patients 5 years later. The specific oxidative activity (oxidative activity related to mass) of CP was calculated in PD and DS. In AD and PD the oxidative activity of CP and SOD1 activity was significantly lower in patients than controls. The specific oxidative activity of CP was also significantly lower in PD patients. The difference in all parameters determined was still present 5 years later in PD patients. There was no difference in the concentration or activity of CP in patients with DS and controls. Because of the gene-dose effect (the gene for SOD1 is located on chromosome 21); the SOD1 activity was 50% higher in the patients than the controls. The CP specific oxidative activity and SOD1 activity were found to be significantly lower in the older (>40 years) than the younger DS patients. Whether changes in CP and SOD1 in AD, PD and DS are primary changes or a result of prolonged disease burden needs to be examined.
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PMID:Case-control studies on ceruloplasmin and superoxide dismutase (SOD1) in neurodegenerative diseases: a short review. 2085 26

Micronuclei (MNi) can originate either from chromosome breakage or chromosome malsegregation events and are therefore ideal biomarkers to investigate genomic instability. Studies in peripheral lymphocytes of patients with neurodegenerative diseases, mainly Alzheimer's disease (AD) and Parkinson's disease (PD), revealed an increased micronucleus (MN) frequency in both disorders but originating mainly from chromosome malsegregation events in AD and from chromosome breakage events in PD. Studies in other neurodegenerative diseases are largely missing, and some data in premature ageing disorders characterised by neurodegeneration and/or neurological complications, such as Ataxia telangiectasia, Werner's syndrome, Down's syndrome (DS) and Cockayne's syndrome, indicate that MNi increase with ageing in cultured cells. An increased frequency of aneuploidy characterises several tissues of AD patients, as well as of individuals at increased risk to develop AD, such as mothers of DS individuals and DS subjects themselves. The use of the buccal MN cytome assay in AD and DS subjects allowed finding significant changes in the MN frequency as well as other cellular modifications reflecting reduced regenerative capacity compared to age- and gender-matched controls. These changes in buccal cytome ratios may prove useful as potential future diagnostics to identify individuals of increased risk for these disorders.
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PMID:Association of micronucleus frequency with neurodegenerative diseases. 2116 87

In the past 5 years, several leading groups have attempted to explain why individuals with Down's syndrome have a reduced risk of many solid tumours and an increased risk of leukaemia and testicular cancer. Niels Bohr, the Danish physicist, noted that a paradox could initiate progress. We think that the paradox of a medical disorder protecting against cancer could be formalised in a new model of inverse cancer morbidity in people with other serious diseases. In this Personal View, we review evidence from epidemiological and clinical studies that supports a consistently lower than expected occurrence of cancer in patients with Down's syndrome, Parkinson's disease, schizophrenia, diabetes, Alzheimer's disease, multiple sclerosis, and anorexia nervosa. Intriguingly, most comorbidities are neuropsychiatric or CNS disorders. We provide a brief overview of evidence indicating genetic and molecular connections between cancer and these complex diseases. Inverse comorbidity could be a valuable model to investigate common or related pathways or processes and test new therapies, but, most importantly, to understand why certain people are protected from the malignancy.
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PMID:No paradox, no progress: inverse cancer comorbidity in people with other complex diseases. 2149 15

Seborrhoeic dermatitis is a frequent chronic inflammatory dermatosis characterized by erythematous patches surmounted by fatty and yellowish scales, affecting particularly the scalp, the naso-labial folds and the eyebrows. Its etio-pathogeny is still not clear, but Malassezia type yeast appear to play a very important role in its development. Several conditions can be associated with high prevalency of seborrhoeic dermatitis (HIV, Parkinson's disease, Down's Syndrome). No curative treatment is available yet, but nevertheless the symptomatology can be controlled, mainly with topical treatments, and particularly antifungals. This article will develop first clinical and pathological aspects of the disease, then propose therapeutic recommendations based on evidences from the literature.
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PMID:[Seborrhoeic dermatitis: clinical manifestations and management]. 2156 97

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of mi- RNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly onto center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress.
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PMID:MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases. 2219 6

The pathological hallmark of neurodegeneration is presence of intra- and extra neuronal inclusion bodies such as Lewy bodies in Parkinson's disease, senile plaques and neurofibrillary tangles in Alzheimer's disease. These are consisted of aggregated conformationally abnormal proteins. The precise mechanism of aggregation remains unknown, but increased expression of aggregation-prone proteins can lead to their aggregation. For example, in Down syndrome, duplication of the 21(st) chromosome, which contains the amyloid beta precursor protein (APP) gene, leads to accumulation of amyloid beta and Alzheimer's disease pathology and multiplication of APP gene is shown to be the cause of familial Alzheimer's disease. Moreover, in rare cases of PD, duplication or triplication of SNCA gene leads to alpha-synuclein accumulation, with triplication producing a more severe phenotype than duplication, suggesting that SNCA expression level determines the severity of the pathology. Lastly, animal models of neurodegenerative disorders are generated by over-expression of causal genes, further supporting the conclusion that increased gene expression is related to pathogenesis. Additional evidence indicates that SNCA promoter polymorphisms increases alpha-synuclein expression and increases susceptibility to sporadic PD. In addition to promoter polymorphisms, epigenetic modification can alter downstream gene expression. Epigenetic regulation includes histone modification and DNA methylation, of which CpG island methylation can be gene-specific; in several different cancers, CpG methylation inhibits binding of the transcription machinery, causing silencing of a specific oncogene, which leads to carcinogenesis. In central nervous system disorders, CpG methylation has been associated with psychiatric disorders, such as autism and schizophrenia. We found several cases of Parkinson's disease with epigenetic abnormality in SNCA gene. Thus, we believe that studying epigenetics can provide previously unknown causes for dementia and other neurodegenerative disorders.
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PMID:["Atypical" method for understanding dementia. How can studying epigenetics contribute?]. 2227 21


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