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)

We report that exposure of cultured, postmitotic chick-embryo sympathetic neurons, to physiological concentrations of dopamine (0.1-1 mM) for 24 h initiates a cellular death process characteristic of apoptosis (= programmed-cell-death, PCD). Dopamine caused marked morphological alterations, mainly axonal disintegration and severe shrinkage and condensation of cell bodies. Flow-cytometric analysis of propidium-iodide-stained cell nuclei revealed the characteristic apoptotic nuclear fragmentation: increase in nuclear granularity and emergence of a large, distinct population of nuclei with reduced DNA content (subdiploid, apoptotic peak). These alterations were similar to changes induced by nerve growth factor (NGF) deprivation, a model of sympathetic neuronal PCD. Alterations were inhibited by the anti-oxidative agent DTT. Inappropriate, dopamine-induced activation of PCD might have a role in nigral neuronal degeneration in Parkinson's disease.
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PMID:Dopamine induces apoptosis-like cell death in cultured chick sympathetic neurons--a possible novel pathogenetic mechanism in Parkinson's disease. 804 91

1. The monoamines dopamine (DA), norepinephrine (NE), epinephrine (E), and serotonin (5-HT) serve as endogenous neurotransmitters in the nervous system. We recently reported that the neurotransmitter DA can trigger apoptosis (programmed cell death; PCD) in cultured, postmitotic chick embryo sympathetic neurons, suggesting a role for apoptosis in degenerative processes such as Parkinson's disease (PD). However, PD is also associated with involvement of other monoaminergic (MA) neuronal systems (noradrenergic and serotoninergic), though to a lesser extent. 2. We therefore tested the apoptosis-triggering potential of NE, E, and 5-HT in comparison to the DA effect, in cultured postmitotic nerve growth factor (NGF)-dependent chick embryo sympathetic neurons and mouse cerebellar granule cells. 3. In both model systems MA induced neuronal attrition characteristic of apoptosis. MA caused marked morphological alterations: severe neuronal soma shrinkage, membrane blebbing, nuclear condensation and fragmentation, and axonal disintegration. Flow-cytometric analysis of propidium iodide-stained cell nuclei revealed characteristic apoptotic nuclear fragmentation. MA-induced apoptosis could be blocked by SH-group containing antioxidants but not by inhibitors of transcription and translation. 4. Comparison between the two model systems revealed that the cerebellar granule neurons were distinctly more sensitive to the neurotoxic potential of the MA than sympathetic neuronal cells. Significant differences in the dose dependencies and time course of the apoptotic effect were observed among the examined MA, graded as DA > NE approximately E > 5-HT. 5. We conclude that the apoptosis triggering potential, probably mediated by oxidative metabolites, is shared by all MA tested, but with differential time course and dose dependencies. A correlation can be drawn between the effects of DA vs NE vs 5-HT and the relative involvement of dopaminergic/noradrenergic/serotoninergic pathways in PD, which may suggest a common multisystem underlying abnormality in neuronal apoptosis-control mechanisms.
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PMID:Monoamine-induced apoptotic neuronal cell death. 911 2

The formation of the hand during embryogenesis, the peeling of sunburned skin and the tremor associated with Parkinson's disease all result from a common process: cell death. Cell death occurs throughout the life span of the organism and represents the ultimate differentiative decision made by cells. Insight into the process of cell death will not only contribute to our understanding of basic developmental issues, but will also facilitate the development of therapeutic interventions that could alter the course of disease. Since all cells have the genetic machinery required to commit suicide, the ability to initiate it in a lineage-specific, non-inflammatory manner would allow for the irradication of specific cancers. Alternatively, inhibition of cell death pathways could rescue valuable but condemned cells, such as HIV infected CD4+ T cells or dopaminergic neurons in Parkinson's disease. The goal of this chapter is to provide both an overview of the basic principles that govern the cellular and molecular mechanisms mediating cell death, as well as serve as a reference of known examples of PCD and the genes that mediate this process.
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PMID:Programmed cell death during animal development. 937 38

A case complicated with colorectal and prostate cancers in paraneoplastic(subacute)cerebellar degeneration(PCD)is extremely rare. We report a retrospective case of rectal carcinoma with paraneoplastic cerebellar degeneration. A 79-year-old man with Parkinson's disease was unable to walk because of paralysis. Brain MRI showed cerebellar atrophy. He was admitted to our hospital for anal bleeding and was diagnosed with colon cancer. An associated diagnosis of PCD was made. After resection, his paralysis and dysarthria were resolved to the extent of beingable to walk and speak fluently. Brain MP-RAGE showed no findings suggestive of metastasis or atrophy. He was treated surgically, which resulted in a transient improvement in PCD symptoms. Per blood testing, cytokines IL-6 and IL-10 were lower postoperatively. Immunosuppressive levels of myeloid- derived suppressor cells(MDSCs)were lower compared with the preoperative values. Thus, innate immunocompetence and resolution of paralysis followed the surgical intervention.
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PMID:[A Case of Rectal Colon Cancer with Paraneoplastic Cerebellar Degeneration]. 3038 61