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)

Adrenal chromaffin cell (ACC) transplants, alone or combined with levodopa treatment, were used in attempted therapy for Parkinson's disease (PD). In a previous study, we demonstrated that levodopa caused chromaffin cell death either by necrosis or by apoptosis in cell culture. Here we report the beneficial effect of a water-soluble derivative of fullerene C(60) (a novel molecule with potent antioxidant properties) and of ascorbic acid when applied to chromaffin cell cultures exposed to levodopa. Both antioxidants remarkably increase the ACC survival and prevent cell death, including apoptosis. Although ACC transplants are not currently considered as an option for PD treatment, these observations should help in exploring the possibilities of preventing the neurotoxicity generated by levodopa and in envisaging new strategies for PD treatment by combining the clinical use of levodopa and potent antioxidants. Chemical properties of fullerene related to biological uses are discussed.
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PMID:Fullerene C60 and ascorbic acid protect cultured chromaffin cells against levodopa toxicity. 1247 20

Adrenal chromaffin cells (ACCs) secrete several neuroactive substances that are effective in influencing pain sensitivity in the central nervous system as well as enhancing the recovery of the intrinsic nigrostriatal dopaminergic system in patients with Parkinson's disease. ACC transplantation may be upregulated by the use of three-dimensional (3-D) scaffolds. In this study, we determined whether biodegradable poly(D,L-lactic-coglycolic acid) (PLGA) (85:15) sponges could be used as support for chromaffin cells. ACCs were isolated from bovine adrenal glands by standard perfusion (95% purity) followed by additional purification (>99.5% purity). ACC (approximately 5 x 10(5) cells) suspension in collagen (type I) was seeded on prewetted sponges and cultured in DMEM-F12 (1:1) medium (5% fetal bovine serum). The catecholamine and enkephalin levels of the samples were measured by high-performance liquid chromatography and radioimmunoassay. Cell morphology was examined by transmission electron microscopy. Morphological evidence showed prolonged viability of chromaffin cells on scaffolds having pores of 250-400 microm. Cell counts and scanning electron microscopy demonstrated that the majority of seeded cells were located within the scaffold. Chromaffin cells exhibited higher levels of enkephalins and catecholamines on PLGA scaffold compared with their monolayer cultures. By the use of 3-D PLGA as support for ACCs, it is possible to upregulate metabolic function and localize a high number of morphologically healthy-looking cells. Highly purified ACCs cultured on PLGA scaffold may have promise in transplantation studies, because these cells are less immunogenic and may be applied to in vivo settings by using short-term immunosuppression.
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PMID:Functional and morphological characteristics of bovine adrenal chromaffin cells on macroporous poly(D,L-lactide-co-glycolide) scaffolds. 1463 88

Adrenal chromaffin cells constitute one of the first cell types to have been defined as a neuroendocrine cell type. Since they produce dopamine, these cells have been proposed for the treatment of neuronal deficits in human Parkinson's disease. However, the factors involved in the development of chromaffin cells are still poorly understood. Based on recent insights from stem cell research, we decided to study the role of extracellular matrices, growth factors and neuropeptides on the neuroendocrine differentiation in a serum-free medium of PC12 cells. Employing immunohistochemistry, quantitative PCR and HPLC analysis, neuroendocrine differentiation was determined by evaluating neurite outgrowth, catecholamine biosynthesis and release as well as neuropeptide and vesicular protein mRNA expression. The combination of bFGF, NGF and PACAP could prevent the inhibition of neurite process development induced by dexamethasone in PC12 cells cultured on ECM. Whereas glucocorticoids were essential in the regulation of enzymes of catecholamine biosynthesis and metabolism, growth factors and PACAP were more efficient in inducing neuropeptide and chromogranin B expression as well as release of dopamine and 3-methoxytyramine. Therefore, in addition to glucocorticoids, chromaffin cells need a gradient of matrix, growth factors, and neuropeptides to develop the full functional phenotype of a neuroendocrine cell.
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PMID:Combinatorial code of growth factors and neuropeptides define neuroendocrine differentiation in PC12 cells. 1463 5

According to estimates made by WHO, approximately 105 million people are affected worldwide by glaucoma. This can be defined as progressive optic neuropathy with structural damage of the optic nerve head and death of retinal ganglion cells. Although elevated IOP is considered responsible for glaucoma, lowering the pressure often does not result in improvement. For this reason, other etiological factors are presumed, which are presented in the following contribution. The role of neuroprotective agents in the treatment of glaucoma is discussed. The pattern of ganglion cell death specific to glaucoma seems to suggest that certain ganglion cells could be more sensitive than others. The theory of "cumulative damage" in this case includes the hypothesis that the delayed onset of many neurodegenerative diseases such as glaucoma, Alzheimer's disease, or Parkinson's disease can be attributed to the age-related accumulation of toxic substances in the ganglion cells. On the contrary, the theory of "singular damage" is based on the assumption that certain ganglion cells are in a state of reduced homeostasis caused by the expression of so-called mutant response genes. Therapeutic approaches worthy of consideration based on their side effect profile and efficacy in animal trials, are presented.
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PMID:[Neuroprotection against glaucoma remains a concept]. 1549 Jan 85

Sympathoadrenal (SA) cell lineage encompasses neural crest derivatives such as sympathetic neurons, small intensely fluorescent (SIF) cells of sympathetic ganglia and adrenal medulla, and chromaffin cells of adrenal medulla and extra-adrenal paraganglia. SA autografts have been used for transplantation in Parkinson's disease (PD) for three reasons: (i) as autologous donor tissue avoids graft rejection and the need for immunosuppressant therapy, (ii) SA cells express dopaminotrophic factors such as GNDF and TGFbetas, and (iii) although most of SA cells release noradrenaline, some of them are able to produce and release dopamine. Adrenal chromaffin cells were the first SA transplanted cells in both animal models of PD and PD patients. However, these autografts have met limited success because long-term cell survival is very poor, and this approach is no longer pursued clinically. Sympathetic neurons from the superior cervical ganglion have been also grafted in PD animal models and PD patients. Poor survival into brain parenchyma of grafted tissue is a serious disadvantage for its clinical application. However, cultured sympathetic cell grafts present a better survival rate, and they reduce the need for levodopa medication in PD patients by facilitating the conversion of exogenous levodopa. SA extra-adrenal chromaffin cells are located on paraganglia (i.e., the Zuckerkandl's organ), and have been used for grafting in a rodent model of PD. Preliminary results indicate that long-term survival of these cells is better than for other SA cells, exerting a more prolonged restorative neurotrophic action on denervated host striatum. The ability of SA extra-adrenal cells to respond to hypoxia, differently to SA sympathetic neurons or adrenal medulla cells, could explain their good survival rate after brain transplantation.
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PMID:Cells of the sympathoadrenal lineage: biological properties as donor tissue for cell-replacement therapies for Parkinson's disease. 1611 61

PART I DESCRIBES IMPORTANT CONTRIBUTIONS MADE BY SOME JAPANESE PIONEERS IN THE FIELD OF NEUROTRANSMITTERS: (their achievements in parentheses) J. Takamine (isolation and crystallization of adrenaline); K. Shimidzu (early hint for acetylcholine as a neurotransmitter); F. Kanematsu (donation of the Kanematsu Memorial Institute in Sydney); T. Hayashi (discovery of the excitatory action of glutamate and the inhibitory action of GABA); and I. Sano (discovery of a high concentration of dopamine in striatum, its reduction in a patient with Parkinson's disease and the treatment with DOPA). In Part II, I present some of my reflections on my research on neurotransmitters. The work of my colleagues and myself has made some significant contributions to the establishment of neurotransmitter roles played by GABA and substance P, the first amino acid and the first peptide neurotransmitters, respectively. By the early 1960s, 3 substances, i.e., acetylcholine, noradrenaline, and adrenaline, had been established as neurotransmitters. Now the number of neurotransmitters is believed to be as many as 50 or even more mainly due to the inclusion of several amino acids and a large number of peptide transmitters.
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PMID:Contributions to the field of neurotransmitters by Japanese scientists, and reflections on my own research. 2401 84

Parkinson's disease has been the object of several therapeutic strategies based upon replacement of the degenerating dopaminergic neurons. Adrenal medullary transplants were tried initially, because of the biochemical relationship between chromaffin cells of the medulla and dopaminergic neurons of the substantia nigra. Compared to transplant of fetal neurons, autologous grafts of adrenal medullary tissue has the advantage of using a readily available source of tissue without the problems of immunosuppression. However, these cells have not proven to be as effective as fetal neurons, probably because they do not fully differentiate into neurons. In animal models, brief treatment with nerve growth factor can facilitate such differentiation. This study is a clinical evaluation of the efficacy of adrenal medullary cell transplantation, combined with nerve growth factor infusion. Two patients were selected who were moderately to severely affected (Hoehn-Yahr stage 2 in on-phase and stage 4 in off-phase). After adrenalectomy, small pieces of medulla were prepared and implanted stereotactically into the dorsal putamen on one side of the brain. A catheter filled with mouse beta-nerve growth factor (NGF) was placed close to the grafts. Infusion of NGF was continued for one month. Despite a progressively deteriorating course prior to surgery, both patients showed improvement on the rating scales postoperatively. There was also significant improvement in timed motor tests. Motor readiness evoked potentials showed increased voltage over the operated hemisphere. The study points to methods and feasibility of supplying nerve growth factor intraparenchymally to the human brain. Possible implications with respect to other growth factors, particularly Glial cell-line Derived Neurotrophic factor (GDNF) are discussed.
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PMID:Long-term beneficial effects of adrenal medullary autografts supported by nerve growth factor in Parkinson's disease. 2428 25

Epinephrine (E) and sympathetic nerve stimulation were described by Thomas Renton Elliott in 1905 for the first time. Dopamine (DA), norepinephrine (NE), E, and serotonin (5-HT) belong to the classic biogenic amines (or monoamines). Parkinson's disease (PD) is among the diseases in which it has been established that catecholamines may account for the neurodegeneration of central and peripheral catecholamine neural systems. PD is a chronic and progressive neurological disorder characterized by resting tremor, rigidity, and bradykinesia, affecting 2% of individuals above the age of 65 years. This disorder is a result of degeneration of DA-producing neurons of the substantia nigra and a significant loss of noradrenergic neurons in the locus coeruleus. In PD and other related neurodegerative diseases, catecholamines play the role of endogenous neurotoxins. Catechol-O-methyltransferase (COMT) and/or monoamine oxidase (MAO) catalyze the metabolism of monoamines. However, the monoamine transporters for DA, NE, and 5-HT namely DAT, NET, and SERT, respectively regulate the monoamine concentration. The metabolism of catecholamines and 5-HT involves common factors. Monoamine transporters represent targets for many pharmacological agents that affect brain function, including psychostimulators and antidepressants. In PD, polymorphisms of the COMT, MAO, DAT, NET, and 5- HTT genes may change the levels of biogenic amines and their metabolic products. The currently available therapies for PD improve the symptoms but do not halt the progression of the disease. The most effective treatment for PD patients is therapy with L-dopa. Combined therapy for PD involves a DA agonist and decarboxylase, MAOs and COMT inhibitors, and is the current optimal form of PD treatment maintaining monoamine balance.
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PMID:Polymorphism of the COMT, MAO, DAT, NET and 5-HTT Genes, and Biogenic Amines in Parkinson's Disease. 2453 84


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