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)

There is substantial evidence based on well designed epidemiologic studies for low cancer rates in patients with Parkinson disease (PD). This risk reduction cannot be attributed to the recognized low life-long incidence of smoking in patients with PD, as not only smoking-related cancers but also non-smoking-related ones are less common in PD. Whereas the risk for most cancers appears to be relatively low in patients with PD, breast cancer and melanomas occur more frequently in the PD population as compared with controls. The relationship between this peculiar pattern of cancer rates and PD might be related to the involvement of common genes in both diseases. Mutations in parkin gene, for example, have been reported in several types of cancer. Furthermore, genes involved in familial forms of PD appear to be abnormally expressed in cancers. Thus, parkin and PINK1 might be tumor suppressor genes, whereas DJ-1 is an oncogene. Cell survival signals may differ owing to mutated genes and represent two opposite extremes such as cell proliferation in cancer and cell death due to apoptosis in PD. Unraveling the link between PD and cancer may open a therapeutic window for both diseases.
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PMID:Are Parkinson disease patients protected from some but not all cancers? 1900 Dec 59

It has been well accredited that the neural stem cells (NSCs) derived from bone marrow stroma cells (BMSCs) can be used as the therapeutic application. However, their efficacy and safety in therapeutic application are uncertain. In this experiment, the trace marking and oncogenicity of NSCs derived from BMSCs (BMSCs-D-NSCs) were studied. The BMSCs were harvested by gradient centrifugation and cultured in "NSCs medium" in vitro. The verified CD133/Nestin-positive BMSCs-D-NSCs were then transplanted into nude mice to detect the oncogenicity, into the right lateral cerebral ventricle or right caudae putamen and substantia nigra to examine, whether the symptoms were improved in Parkinson's Disease (PD) models after transplantation, by both SPECT image assay of dopamine transporter (DAT) in corpus striatum and its average standard uptake value (SUVave) in corpus striatum and thalamus. Tissue samples and surviving model animals were studied at 1, 3, and 6 months post-transplantation. Before transplantation, the cells were labeled with BrdU or rAAV-GFP for the pathological sections, and with Feridex for the in vivo trace by MRI assay. The concanavalin A (ConA) agglutination test, stop-dependence test with soft agar, karyotype analysis of chromosome G zone in BMSCs-D-NSCs, and the nude mouse neoplasia test were also performed. The BrdU, rAAV-GFP or Feridex can be used as trace markers of BMSCs-D-NSCs during transplantation. The transplanted BMSCs-D-NSCs displayed neither toxicity nor neoplasia up to 6 months in vivo, but could play an important role in improving the symptoms of the animals with degenerative diseases like PD.
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PMID:Experimental study on trace marking and oncogenicity of neural stem cells derived from bone marrow. 1780 59

WW domain-containing oxidoreductase (named WWOX, FOR or WOX1) is a pro-apoptotic protein and tumor suppressor. Animals treated with dopaminergic neurotoxin 1-methyl-4-phenyl-pyridinium (MPP+) develop Parkinson's disease (PD)-like symptoms. Here we investigated whether WOX1 is involved in MPP+-induced neurodegeneration. Upon insult with MPP+ in rat brains, WOX1 protein was upregulated and phosphorylated at Tyr33 (or activated) in the injured neurons in the striatum and cortex ipsilaterally to intoxication, as determined by immunohistochemistry and Western blotting. Also, WOX1 was present in the condensed nuclei and damaged mitochondria of degenerative neurons, as revealed by transmission immunoelectron microscopy. Time-lapse microscopy revealed that MPP+ induced membrane blebbing and shrinkage of neuroblastoma SK-N-SH cells. Dominant-negative WOX1, a potent inhibitor of Tyr33 phosphorylation, abolished this event, indicating a critical role of the phosphorylation in apoptosis. c-Jun N-terminal kinase (JNK1) is known to bind and counteract the apoptotic function of WOX1. Suppression of JNK1 function by a dominant-negative spontaneously induced WOX1 activation. WOX1 physically interacted with JNK1 in SK-N-SH cells and rat brain extracts. MPP+ rapidly increased the binding, followed by dissociation, which is probably needed for WOX1 to exert apoptosis. We synthesized a short Tyr33-phosphorylated WOX1 peptide (11 amino acid residues). Interestingly, this peptide blocked MPP+-induced neuronal death in the rat brains, whereas non-phospho-WOX1 peptide had no effect. Together, activated WOX1 plays an essential role in the MPP+-induced neuronal death. Our synthetic phospho-WOX1 peptide prevents neuronal death, suggestive of its therapeutic potential in mitigating the symptoms of PD.
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PMID:MPP+-induced neuronal death in rats involves tyrosine 33 phosphorylation of WW domain-containing oxidoreductase WOX1. 1837 Oct 80

The long-term goal of nuclear transfer or alternative reprogramming approaches is to create patient-specific donor cells for transplantation therapy, avoiding immunorejection, a major complication in current transplantation medicine. It was recently shown that the four transcription factors Oct4, Sox2, Klf4, and c-Myc induce pluripotency in mouse fibroblasts. However, the therapeutic potential of induced pluripotent stem (iPS) cells for neural cell replacement strategies remained unexplored. Here, we show that iPS cells can be efficiently differentiated into neural precursor cells, giving rise to neuronal and glial cell types in culture. Upon transplantation into the fetal mouse brain, the cells migrate into various brain regions and differentiate into glia and neurons, including glutamatergic, GABAergic, and catecholaminergic subtypes. Electrophysiological recordings and morphological analysis demonstrated that the grafted neurons had mature neuronal activity and were functionally integrated in the host brain. Furthermore, iPS cells were induced to differentiate into dopamine neurons of midbrain character and were able to improve behavior in a rat model of Parkinson's disease upon transplantation into the adult brain. We minimized the risk of tumor formation from the grafted cells by separating contaminating pluripotent cells and committed neural cells using fluorescence-activated cell sorting. Our results demonstrate the therapeutic potential of directly reprogrammed fibroblasts for neuronal cell replacement in the animal model.
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PMID:Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. 1839 Nov 96

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of midbrain dopaminergic (DA) neurons and a subsequent reduction in striatal dopamine. As a treatment for advanced Parkinson's disease, deep brain stimulation (DBS) of the thalamus was introduced in 1987 to treat tremor, and was applied in 1993 to the subthalamic nucleus. Now high-frequency stimulation of the subthalamic nucleus has become a surgical therapy of choice. Another surgical treatment is a cell replacement therapy. Transplantation of fetal dopaminergic (DA) neurons can produce symptomatic relief, however, the technical and ethical difficulties in obtaining sufficient and appropriate donor fetal brain tissue have limited the application of this therapy. Then, neural precursor cells and embryonic stem (ES) cells are expected to be candidates of potential donor cells for transplantation. We induced DA neurons from monkey ES cells, and analyzed the effect of transplantation of the DA neurons into MPTP-treated monkeys as a primate model of Parkinson's disease. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons, attenuating the MPTP-induced neurological symptoms. DA neurons have also been generated from several human ES cell lines. Furthermore, functional recovery of rat PD models after transplantation was observed. One of the major problems in ES cell transplantation is tumor formation, which is caused by a small fraction of undifferentiated ES cells in the graft. So, it is essential for undifferentiated ES cells to be eliminated from the graft in order for transplantation to be feasible. These efforts will lead to clinical application of ES cell transplantation to the patients with PD.
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PMID:[Neuromodulation for Parkinson's disease]. 1845 54

Deep brain stimulation (DBS) has been shown to be a safe and effective method for the treatment of refractory Parkinson's disease and other movement disorders. Traditionally, frame-based stereotactic have been the standard technique commonly used for DBS surgery. With the development of image-guided neurosurgical systems, frameless stereotactic has been increasingly used for tumor resection or biopsy without the use of stereotactic frame. Frameless stereotactic for functional surgery has been recently developed with the accuracy comparable to frame-based stereotactic surgery. The authors report the surgical technique of frameless functional stereotactic for the treatment of movement disorders.
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PMID:Frameless stereotactic for deep brain stimulation placement: operative technique. 1855 58

Many diseases are easier to treat and control when detected at an early stage of disease progression. Often, disease-related antigens or biomarkers are shed from the primary site and present in the blood. Unfortunately, there are very few tests capable of detecting these rare biomarkers in the blood. A blood test would be very useful to diagnose the disease earlier, monitor effectiveness of treatments, predict recurrence, and monitor recurrence. There is certainly a need to develop assays that are ultra-sensitive, non-invasive, and high-throughput. Here we describe several highly sensitive immunological assays we have developed to detect rare serum antigens. Initially we created an assay named immuno-detection amplified by T7 RNA polymerase (IDAT). To enhance the effectiveness and streamline the procedure, this assay was amended to the facile amplification system termed fluorescent amplification catalyzed by T7 polymerase technique (FACTT). These assays have been used to analyze the tumor antigen HER2 and the prion protein PrPSc. They can also be applied to other tumor markers or antigens from a variety of diseases such as cardiovascular disease, rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, and hepatitis. These tests are not limited to testing only serum, but may also be applicable to detecting biomarkers in tissue, saliva, urine, cerebrospinal fluid, etc. Clearly, the FACTT-based technology represents an important step in the detection of rare molecules in fluids or tissues for a variety of diseases.
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PMID:Non-invasive, ultra-sensitive, high-throughput assays to quantify rare biomarkers in the blood. 1857 45

We describe a case with right hemiparkinsonism due to a frontal meningioma with surrounding edema compressing the basal ganglia. The initial diagnosis of idiopathic Parkinson's disease (PD) was made in another institution on the basis of the positive family history, the clinical symptoms and the asymmetric reduction of striatal tracer binding in a single photon emission computed tomography study for the dopamine transporter. The symptoms of parkinsonism resolved completely shortly after surgery for removal of the tumor. This case points to the significance of structural neuroimaging in the evaluation of parkinsonism even in cases that fulfill all the necessary clinical criteria for idiopathic PD.
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PMID:Hemiparkinsonism due to frontal meningioma. 1857 86

Dysregulation of genes that control cell-cycle progression and DNA repair is a hallmark of tumorigenesis. It is becoming increasingly apparent, however, that these defects also contribute to degeneration of post-mitotic neurons under certain conditions. The gene for ataxia-telangiectasia mutated (ATM) is a prototype for this dual mechanism of action, with loss-of-function mutations causing not only selective degeneration of cerebellar neurons but also increased susceptibility to breast cancer and hematologic malignancy. Increased dosage of amyloid precursor protein in Down syndrome (trisomy 21) predisposes to dementia of Alzheimer type and may also contribute to acute leukemia and transient myeloproliferative disorder. The gene parkin, loss-of-function mutations in which account for about half of cases of early-onset Parkinson disease, has been identified as a candidate tumor suppressor gene by several groups. Parkin is deleted or downregulated in several tumor types, and its re-expression sensitizes derivative cell lines to inhibitors of cell-cycle progression. The overlap of molecular pathways implicated in cancer and neurodegeneration challenges long-held notions about differentiated cellular states and may open the door to novel therapeutic approaches to both groups of disorders.
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PMID:Tumorigenesis and neurodegeneration: two sides of the same coin? 1862 69

Tissue culture of immortal cell strains from diseased patients is an invaluable resource for medical research but is largely limited to tumor cell lines or transformed derivatives of native tissues. Here we describe the generation of induced pluripotent stem (iPS) cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance; these diseases include adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID), Shwachman-Bodian-Diamond syndrome (SBDS), Gaucher disease (GD) type III, Duchenne (DMD) and Becker muscular dystrophy (BMD), Parkinson disease (PD), Huntington disease (HD), juvenile-onset, type 1 diabetes mellitus (JDM), Down syndrome (DS)/trisomy 21, and the carrier state of Lesch-Nyhan syndrome. Such disease-specific stem cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation and drug development.
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PMID:Disease-specific induced pluripotent stem cells. 1869 44


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