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)

Fetal neural grafts, rich in dopamine neurons, taken from the ventral mesencephalon and implanted into the dopamine-denervated striatum, can reinnervate the striatum, form synaptic contacts with host neurons, release dopamine and improve motor function. In animal models of Parkinson's disease, the improvement resulting from transplantation is dependent on the number of surviving grafted dopamine neurons and the density and extent of graft-derived reinnervation. The major unresolved scientific question at present is not whether neural grafting is better than established drug treatments but if survival and function of such grafts are at all possible in patients with Parkinson's disease. A more general problem is that if cell transplantation is to become clinically useful for a large number of Parkinsonian patients and also be applied in other neurological disorders, alternative sources of donor tissue must be found; several have been proposed, including adrenal medulla cells and sympathetic ganglia but perhaps the most exciting strategy is to implant cells that have been genetically engineered to synthesize and release L-dopa or dopamine.
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PMID:Clinical application of neuronal grafts in Parkinson's disease. 769 11

The low availability of dopamine containing neurons for grafting in Parkinson's disease is a general problem. Free-floating roller tube (FFRT) cultures allow storage of fetal mesencephalic tissue prior to transplantation. Preoperative functional testing permits to select an optimized set of individual cultures for transplantation. Rat fetal ventral mesencephali (E13) were dissected out and divided into four equally sized pieces each and individually prepared as FFRT cultures. After 4, 8, 12, and 16 days in vitro (DIV) the medium of each culture was collected during routine medium change and immediately stabilized. Dopamine was extracted and probes were determined with reversed phase HPLC using electro-chemical detection. After 16 DIV cultures were fixed and cell counts performed in tyrosine hydroxylase (TH)-immunostained serial sections. The mean dopamine content +/- SEM In culture conditioned media was at 4 DIV: 21 +/- 2 pg, n = 38; at 8 DIV: 37 +/- 4 pg, n = 40; at 12 DIV: 52 +/- 7 pg, n = 38; and at 16 DIV: 39 +/- 5 pg, n = 38. In all cultures devoid of dopamine after 4 and 8 DIV (12.5%) levels remained below detectability at 12 and 16 DIV. Cultures derived from the rostral mesencephalon showed significantly higher dopamine values than those from the caudal mesencephalon at 12 DIV. The mean number of TH-immunoreactive (-ir) cells/culture +/- SEM after 16 DIV was 556 +/- 51, n = 40. The correlation between TH-ir cell number (CN) and dopamine content of rostrally derived cultures at 16 DIV was: CN = 7.4 (dopamine [pg]) + 248; R = 0.75; n = 19; p < 0.001. No dopamine was present in cultures without TH-ir cells. These results demonstrate that sequential noninvasive screening of dopamine in single cultures is feasible and that the dopamine content is correlated to the number of surviving TH-ir cells. This permits to select cultures rich in dopaminergic neurons for transplantation.
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PMID:Noninvasive dopamine determination by reversed phase HPLC in the medium of free-floating roller tube cultures of rat fetal ventral mesencephalon: a tool to assess dopaminergic tissue prior to grafting. 888 83

Our ability to track the progression of neurological disorders like Parkinson's disease (PD) is hampered by a lack of biomarkers, rendering the neuronal changes that underlie clinical symptoms largely a mystery. In this issue of the JCI, Fanara et al. report the development of an innovative approach to biomarker development. They describe a method to measure axonal microtubule function via cerebrospinal fluid (CSF) sampling and use this technique to provide evidence of deficiencies in this process in PD patients. This both sheds light on the pathophysiology of PD and has implications for the more general problem of developing biomarkers for any brain process.
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PMID:Mining the secrets of the CSF: developing biomarkers of neurodegeneration. 2292 54