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)

At has been reported that transplantation of appropriate cells, growth factors, and/or extracellular matrix may help the regeneration of damaged tissues or organs. Some growth factors, such as basic fibroblast growth factor(bFGF), have been successfully transferred to patients with ischemic heart disease. Embryonic dopamine neurons were also transplanted into the brains of patients with Parkinson's disease successfully. We have also performed cultured auto iris pigment epithelial cell (IPE) transplantation into the subretinal space after removal of choroidal neovascularization in patients with age-related macular degeneration (AMD). Here, we report the results of auto IPE transplantation in 35 patients, who could be followed for more than 6 months. We also tried to apply cell transplantation to other retinal diseases by managing the transplanted cells as introduced growth factor genes. Auto IPE transplantation was performed after removal of choroidal neovascular membranes (CNV). Visual acuity wes improved by more than 0.2 log MAR in 18 of 35 patients (51.5%), it was unchanged in 11 patients (31.5%), and it was worsened in 6 patients (17%). No significant difference was observed in comparison to patients who underwent CNV removal only. However, unlike the previous reports, we found no patients showing rejection. We also found that the cultured transplanted cells never showed proliferation under the retina or in the vitreous cavity and concluded that cultured auto IPE transplantation can be performed safely without complications. Next, we examined whether cell transplantation can be expanded to other degenerative retinal diseases. One of our results showed that host RPE may play an important role against the transplanted cells in the subretinal regions. When we introduced bFGF gene into the cells, we found synexpression cluster of the genes in the cells. One of the most prominent movements among the genes was lysyl oxidase like-1 gene, which plays an important role in the maturation of the extracellular collagen and in cell attachment. However, when we examined the cell attachment on the culture plates after 12 hours of culture, no significant difference was observed between the cells with or without bFGF. Further, when we examined the area of the cells transplanted into the subretinal space of rats during successive follow-up using fluorescein marker (EGFP), no statistical significance was observed. The gene expression pattern may be different when we introduce different growth factor gene. No antibody production was generated against the growth factor gene introduced cells after cell transplantation. Further, when we made transgenic mice expressing bFGF or Axokine cDNA in the RPE of rd mice, no photoreceptor degeneration was observed. One of the reasons was suspected to be that bFGF was expressed systemically by the promoter of tyrosinase related-protein 1 gene and may lead to lethality. Another reason was suspected to be suppression of the function of Axokine by the down-regulation of the ciliary neurotrophic factor or its receptor gene. Conversely, when we produced photoreceptor degeneration by constant light damage in the rats, we found partial photoreceptor rescue by transplantation of the growth factor gene introduced RPE. We show here the possibility that growth factor gene introduced cell transplantation may be applied to retinal diseases, if we select appropriate cells and genes.
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PMID:[Regeneration of the retina using pigment epithelial cell transplantation]. 1261 Aug 37

Type-1 interferons (IFNs) are pleiotropic cytokines with a critical role in the initiation and regulation of the pro-inflammatory response. However, the contribution of the type-1 IFNs to CNS disorders, specifically chronic neuropathologies such as Parkinson's disease is still unknown. Here, we report increased type-1 IFN signaling in both post mortem human Parkinson's disease samples and in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model. In response to MPTP, mice lacking the type-1 IFN receptor (IFNAR1(-/-) ) displayed decreased type-1 IFN signaling, an attenuated pro-inflammatory response and reduced loss of dopaminergic neurons. The neuroprotective potential of targeting the type-1 IFN pathway was confirmed by reduced neuroinflammation and DA cell death in mice treated with a blocking monoclonal IFNAR1 (MAR-1) antibody. The MPTP/MAR-1 treated mice also displayed increased striatal dopamine levels and improved behavioural outcomes compared to their MPTP/IgG controls. These data, implicate for the first time, a deleterious role for the type-1 IFNs as key modulators of the early neuroinflammatory response and therefore the neuronal cell death in Parkinson's disease. GLIA 2016;64:1590-1604.
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PMID:Type-1 interferons contribute to the neuroinflammatory response and disease progression of the MPTP mouse model of Parkinson's disease. 2740 46