Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Even though great progress has been made in the clinical characterization of Parkinson's disease, several studies report that the diagnosis of Parkinson's disease is not pathologically confirmed in up to 25% of clinically diagnosed Parkinson's disease. Therefore, tissue collected from clinically diagnosed patients with idiopathic Parkinson's disease can have a high rate of misdiagnosis; hence in vitro studies from such tissues to study Parkinson's disease as a preclinical model can become futile. By collecting postmortem human leptomeninges with a confirmed neuropathological diagnosis of Parkinson's disease and characterized by nigrostriatal cell loss and intracellular protein inclusions called Lewy bodies, one can be certain that clinically observed parkinsonism is not caused by another underlying disease process (e.g. tumor, arteriosclerosis). This protocol presents the dissection and preparation of postmortem human leptomeninges for derivation of a meningeal fibroblast culture. This procedure is robust and has a high success rate. The challenge of the culture is sterility as the brain procurement is generally not performed under sterile conditions. Therefore, it is important to supplement the culture media with a cocktail of penicillin, streptomycin, and amphotericin B. The derivation of meningeal fibroblasts from autopsy-confirmed cases with Parkinson's disease provides the foundation for in vitro modeling of Parkinson's disease. Meningeal fibroblasts appear 3-9 days after sample preparation and about 20-30 million cells can be cryopreserved in 6-8 weeks. The meningeal fibroblast culture is homogenous and the cells express fibronectin, a commonly used marker to identify meninges.
 ...
PMID:Derivation of Leptomeninges Explant Cultures from Postmortem Human Brain Donors. 2819 70

The role of proinflammatory cytokines in cognitive function has been investigated with both beneficial and possible detrimental effects, depending on the cytokine. More recently, the type 2 IL-4 has been demonstrated to play a role in cognition. In this study, using the Morris water maze task, we demonstrate that IL-13-deficient mice are significantly impaired in working memory as well as attenuated reference memory, both functions essential for effective complex learning. During the learning process, wild-type mice increased the number of CD4+ T cells in the meninges and production of IL-13, whereas neither Morris water maze-trained IL-4 nor trained IL-13-deficient mice were able to increase CD4+ T cells in the meninges. Mechanistically, we showed that IL-13 is able to stimulate primary astrocytes to produce brain-derived neurotrophic factor, which does foster cognitive functions. Moreover, Morris water maze-trained wild-type mice were able to increase astrocyte-produced glial fibrillary acidic protein in the hippocampus, which was impaired in Morris water maze-trained IL-4- and IL-13-deficient mice. Collectively, this study strongly suggests that the Th2 cytokines, not only IL-4 but also IL-13, are involved in cognitive functions by stimulating astrocytes from the meninges and hippocampus. These results may be important for future development of therapeutic approaches associated with neurologic disorders such as Parkinson disease-associated dementia and HIV-associated dementia among others.
 ...
PMID:IL-13-Mediated Regulation of Learning and Memory. 2820 15

Magnetic iron oxide nanoparticles, magnetite/maghemite, have been identified in human tissues, including the brain, meninges, heart, liver, and spleen. As these nanoparticles may play a role in the pathogenesis of neurodegenerative diseases, a pilot study explored the occurrence of these particles in the cervical (neck) skin of 10 patients with Parkinson's disease and 10 healthy controls. Magnetometry and transmission electron microscopy analyses revealed magnetite/maghemite nanoparticles in the skin samples of every study participant. Regarding magnetite/maghemite concentrations of the single-domain particles, no significant between-group difference was emerged. In low-temperature magnetic measurement, a magnetic anomaly at ~50 K was evident mainly in the dermal samples of the Parkinson group. This anomaly was larger than the effect related to the magnetic ordering of molecular oxygen. The temperature range of the anomaly, and the size-range of magnetite/maghemite, both refute the idea of magnetic ordering of any iron phase other than magnetite. We propose that the explanation for the finding is interaction between clusters of superparamagnetic and single-domain-sized nanoparticles. The source and significance of these particles remains speculative.
 ...
PMID:Magnetic Nanoparticles in Human Cervical Skin. 3124 75

The discovery of an active lymphatic system in the meninges (dura mater) has opened up a wide range of possibilities for the role of CNS immunoglobulins in brain development in early fetal life or during infancy. The antibody-dependent and -independent functions of B cells in the immunopathogenesis of multiple sclerosis are not new to immunologists, yet their role in other neurodegenerative disorders such as Alzheimer's and Parkinson's disease is incompletely understood. Deep cervical lymph nodes have emerged as a candidate site for autosensitization against CNS antigens and have been shown to provide the right kind of milieu for the dynamic interaction of antigen-presenting cells, B cells, and T cells. The presence of different B cells in the lymph nodes and the production of natural autoantibodies by B-1 cells have definitely unlocked another piece of the puzzle. At a time when CD19 and CD20 monoclonal antibodies have shown remarkable results in ameliorating the relapse and progression of multiple sclerosis, it is imperative to dissect out the diversity in B cell populations inside the CNS to identify new targets to improve current treatment regimens for neurodegenerative diseases. This review highlights the origin, migration, function, and regulation of B cells and the production of intrathecal immunoglobulins considering the previous and current findings and taking into account the differences between a healthy state and the changes that occur during an inflammatory or autoimmune response.
 ...
PMID:Decoding intrathecal immunoglobulins and B cells in the CNS: their synthesis, function, and regulation. 3192 79