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)

Rapid-onset dystonia-parkinsonism (RPD) is an autosomal dominant movement disorder characterized by sudden onset of persistent dystonia and parkinsonism, generally during adolescence or early adulthood. Symptoms evolve over hours or days, and generally stabilize within a few weeks, with slow or no progression. Other features include little or no response to L-dopa, and low levels of homovanillic acid in the central nervous system. Neuroimaging studies indicate no degeneration of dopaminergic nerve terminals in RDP, suggesting that this disorder results from a functional deficit, as in dystonia, rather than neuronal loss, as in Parkinson's disease. We studied 81 members of two midwestern US families with RDP, 16 of whom exhibited classic features of RDP. We found significant evidence for linkage in these two families to markers on chromosome 19q13, with the highest multipoint LOD score at D19S198 (z = 5.77 at theta = 0.0). The flanking markers D19S587 and D19S900 define a candidate region of approximately 8 cM. Although RDP itself is a rare condition, it is important because it has clinical and biochemical similarities to both Parkinson's disease and dystonia. Identification of the genetic defect in RDP holds promise for understanding the underlying disease processes of both of these more common diseases.
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PMID:Rapid-onset dystonia-parkinsonism: linkage to chromosome 19q13. 1044 82

The aim of this study was to investigate the clinical heterogeneity of Parkinson's disease (PD) among a cohort of Chinese patients in early stages. Clinical data on demographics, motor variables, motor phenotypes, disease progression, global cognitive function, depression, apathy, sleep quality, constipation, fatigue, and L-dopa complications were collected from 138 Chinese PD subjects in early stages (Hoehn and Yahr stages 1-3). The PD subject subtypes were classified using k-means cluster analysis according to the clinical data from five- to three-cluster consecutively. Kappa statistical analysis was performed to evaluate the consistency among different subtype solutions. The cluster analysis indicated four main subtypes: the non-tremor dominant subtype (NTD, n=28, 20.3%), rapid disease progression subtype (RDP, n=7, 5.1%), young-onset subtype (YO, n=50, 36.2%), and tremor dominant subtype (TD, n=53, 38.4%). Overall, 78.3% (108/138) of subjects were always classified between the same three groups (52 always in TD, 7 in RDP, and 49 in NTD), and 98.6% (136/138) between five- and four-cluster solutions. However, subjects classified as NTD in the four-cluster analysis were dispersed into different subtypes in the three-cluster analysis, with low concordance between four- and three-cluster solutions (kappa value=-0.139, P=0.001). This study defines clinical heterogeneity of PD patients in early stages using a data-driven approach. The subtypes generated by the four-cluster solution appear to exhibit ideal internal cohesion and external isolation.
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PMID:Clinical heterogeneity in patients with early-stage Parkinson's disease: a cluster analysis. 2188 44

There is no data up to now to show that peptide can deliver plasmid into brain as a single-component transfer vector. Here we show that a novel peptide, RDP (consisted of 39 amino acids), can be exploited as an efficient plasmid vector for brain-targeting delivery. The plasmids containing Lac Z reporter gene (pVAX-Lac Z) and BDNF gene (pVAX-BDNF) are complexed with RDP and intravenously injected into mice. The results of gel retardation assay show that RDP enables to bind DNA in a dose-dependent manner, and the X-Gal staining identity that Lac Z is specifically expressed in the brain. Also, the results of Western blot and immunofluorescence staining of BDNF indicate that pVAX-BDNF complexed with RDP can be delivered into brain, and show neuroprotective properties in experimental Parkinson's disease (PD) model. The results demonstrate that RDP enables to bind and deliver DNA into the brain, resulting in specific gene expression in the neuronal cells. This strategy provides a novel, simple and effective approach for non-viral gene therapy of brain diseases.
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PMID:A novel peptide delivers plasmids across blood-brain barrier into neuronal cells as a single-component transfer vector. 2355 34

The clinical heterogeneity of Parkinson's disease (PD) reveals the presence of several PD subtypes. The objectives of this study were to identify PD subtypes using cluster analysis (CA) and to determine the association between the subtypes and the polymorphisms in LRRK2 (G2385R and R1628P) and GBA (L444P) genes. A k-means CA of demographics, disease progression, motor and non-motor symptoms was performed from 1,510 Chinese PD patients from the Chinese National Consortium on Neurodegenerative Diseases. Pearson correlation analysis was performed to eliminate uninformative characteristics. Blood samples from 852 patients were obtained for genetic analysis of LRRK2 and GBA. Genotypic associations between various subtypes and genetic variants were examined using chi-square test. We identified four different subtypes: subtype 1 was non-tremor dominant (NTD, n=469; 31.1%); subtype 2 had a rapid disease progression with late onset (RDP-LO, n=67; 4.4%); subtype 3 had benign pure motor characteristics (BPM, n=778; 51.5%) without non-motor disturbances; and subtype 4 was tremor dominant with slow disease progression (TD-SP, n=196; 13.0%). Subtypes 1, 2, and 4 had similar mean age of onset. No associations were identified between polymorphisms in LRRK2 (R1628P) and GBA (L444P) genes and the four subtypes (P>0.05).
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PMID:Heterogeneity among patients with Parkinson's disease: cluster analysis and genetic association. 2573 3