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 studied two genetic polymorphisms (240C/T and 480G/A) of the brain-derived neurotrophic factor (BDNF) gene in Japanese patients with Alzheimer's disease (AD, n = 172), Parkinson's disease (PD, n = 327), and multiple system atrophy (MSA, n = 122), as well as controls (n = 275). The distribution of the 240 C/T polymorphism was significantly different between AD patients and controls, whereas there was no difference in the genotype of the two polymorphisms between MSA and controls or between PD and controls. Our data suggest that BDNF might play a role in AD.
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PMID:Brain-derived neurotrophic factor gene polymorphisms in Japanese patients with sporadic Alzheimer's disease, Parkinson's disease, and multiple system atrophy. 1583 55

Ifenprodil, a non-competitive NMDA-receptor antagonist, has been shown to exhibit marked cytoprotective activities in animal models for focal ischemia and Parkinson's disease. To test the hypothesis that the cytoprotective effect is due to the release of neurotrophic factors (NTFs), we examined the effects of ifenprodil on the NTF contents in mouse astrocyte cultures. The results revealed that ifenprodil strongly enhanced the production of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in these cultures. The ifenprodil-induced NGF secretion was found to be partially mediated by the activation of protein kinase C (PKC) and p42/p44 mitogen-activated protein (MAP) kinase cascade pathways. These findings suggest that the cytoprotective effects of ifenprodil are probably attributed to enhanced secretion of these NTFs from astrocytes.
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PMID:Production of NGF, BDNF and GDNF in mouse astrocyte cultures is strongly enhanced by a cerebral vasodilator, ifenprodil. 1584 60

Recent studies have highlighted that female sex hormones represent potential neuroprotective agents against damage produced by acute and chronic injuries in the adult brain. Clinical reports have documented the effectiveness of estrogens to attenuate symptoms associated with Parkinson's disease, and to reduce the risk of Alzheimer's disease and cerebrovascular stroke. This evidence is corroborated by numerous experimental studies documenting the protective role of female sex hormones both in vitro and in vivo. Accordingly, estrogens have been shown to promote survival and differentiation of several neuronal populations maintained in culture, and to reduce cell death associated with excitotoxicity, oxidative stress, serum deprivation or exposure to beta-amyloid. The neuroprotective effects of estrogens have been widely documented in animal models of neurological disorders, such as Alzheimer's and Parkinson's diseases, as well as cerebral ischemia. Although estrogens are known to exert several direct effects on neurones, the cellular and molecular mechanisms implicated in their protective actions on the brain are not completely understood. Thus, on the basis of clinical and experimental evidence, in this review, we discuss recent findings concerning the neuronal effects of estrogens that may contribute to their neuroprotective actions. Both estrogen receptor-dependent and -independent mechanisms will be described. These include modulation of cell death regulators, such as Bcl-2, Akt and calpain, as well as interaction with growth factors, such as BDNF, NGF, IGF-I and their receptors. The anti-inflammatory effects of estrogens will also be described, namely their ability to reduce brain levels of inflammatory mediators, cytokines and chemokines. Finally, a brief overview about receptor-independent mechanisms of neuroprotection will aim at describing the antioxidant effects of estrogens, as well as their ability to modulate neurotransmission.
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PMID:From clinical evidence to molecular mechanisms underlying neuroprotection afforded by estrogens. 1596 77

Both glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) can protect nigrostriatal dopaminergic neurons from neurotoxins in rodent and monkey models of Parkinson's disease (PD). These two neurotrophic factors are usually tested individually. This study was designed to compare GDNF, BDNF, or both, for their capabilities to correct behavioral deficits and protect nigrostriatal dopaminergic neurons in a rat model of PD. Gene transfer used a helper virus-free Herpes Simplex Virus (HSV-1) vector system and a modified neurofilament heavy gene promoter that supports long-term expression in forebrain neurons. Rats received unilateral intrastriatal injections of HSV-1 vectors that express either GDNF or BDNF, or both vectors, followed by intrastriatal injections of 6-hydroxydopamine (6-OHDA). Recombinant GDNF or BDNF was detected in striatal neurons in rats sacrificed at 7 months after gene transfer. Of note, GDNF was significantly more effective than BDNF for both correcting behavioral deficits and protecting nigrostriatal dopaminergic neurons. Expression of both neurotrophic factors was no more effective than expression of only GDNF. These results suggest that GDNF is more effective than BDNF for correcting the rat model of PD, and that there are no detectable benefits from expressing both of these neurotrophic factors.
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PMID:Comparison of the capability of GDNF, BDNF, or both, to protect nigrostriatal neurons in a rat model of Parkinson's disease. 1601 90

The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been shown to promote survival and differentiation of midbrain dopaminergic (DAergic) neurons in vitro and in vivo. This is consistent with their expression and that of their cognate receptors, trkB and trkC, in the nigrostriatal system. Degeneration of DAergic neurons of the substantia nigra and alpha-synuclein-positive aggregates in the remaining substantia nigra (SN) neurons are hallmarks of Parkinson's disease (PD). Reduced expression of BDNF has been reported in the SN from PD patients. Moreover, mutations in the BDNF gene have been found to play a role in the development of familial PD. We show now that haploinsufficiencies of the neurotrophin receptors trkB and/or trkC cause a reduction in numbers of SN neurons in aged (21-23 month old) mice, which is accompanied by a reduced density in striatal tyrosine hydroxylase immunoreactive (TH-ir) fibers. These aged mutant mice, in contrast to wild-type littermates, display an accumulation of alpha-synuclein in the remaining TH-positive neurons of the SN. We conclude that impairment in trkB and/or trkC signaling induces a phenotype in the aged SN, which includes two hallmarks of PD, losses of TH positive neurons and axons along with massive neuronal deposits of alpha-synuclein.
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PMID:Haploinsufficiency for trkB and trkC receptors induces cell loss and accumulation of alpha-synuclein in the substantia nigra. 1603 97

Rasagiline (N-propargyl-1R-aminoindan) is a novel, highly potent, irreversible monoamine oxidase (MAO)-B inhibitor designed for use as an antiparkinsonian drug. Unlike selegiline, rasagiline is not derived from amphetamine or metabolized to neurotoxic l-methamphetamine derivative, and it does not have sympathomimetic activity. Moreover, at selective MAO-B inhibitory dosage, it does not induce a "cheese reaction." Rasagiline is effective as monotherapy or as an adjunct to L-dopa for patients with early and late Parkinson's disease. Adverse events do not occur with greater frequency in subjects receiving rasagiline than in those on placebo. Its S-isomer, TVP1022, is more than a thousand times less potent as an MAO inhibitor. However, both drugs have neuroprotective activities in neuronal cell cultures in response to various neurotoxins, as well as in vivo (e.g., in response to global ischemia, neurotrauma, head injury, anoxia, etc.), indicating that MAO inhibition is not a prerequisite for neuroprotection. The neuroprotective activity of these drugs has been demonstrated to be associated with the propargylamine moiety, which protects mitochondrial viability and mitochondrial permeability transition pore by activating Bcl-2 and downregulating the Bax family of proteins. Rasagiline processes amyloid precursor protein (APP) into the neuroprotective-neurotrophic soluble APPalpha (sAPPalpha) by protein kinase C- and mitogen-activated protein kinase-dependent activation of alpha-secretase, and increases nerve growth factor, glial cell- derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) expression and proteins. Thus, rasagiline may induce neuroprotection, neuroplasticity and long-term potentiation. Rasagiline has therefore been chosen by the National Institutes of Health (NIH) to study its neuroprotective effects in neurodegenerative diseases. Long-term studies are required to evaluate the drug's disease-modifying prospects in Parkinson's and Alzheimer's diseases.
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PMID:Neuropharmacological, neuroprotective and amyloid precursor processing properties of selective MAO-B inhibitor antiparkinsonian drug, rasagiline. 1611 Mar 45

The association between Parkinson's disease (PD) and the G196A polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been investigated in several case-control studies, producing contradictory results: one study indicated that homozygocity of AA is associated with PD, another study produced the opposite result, whereas other studies found no association. To investigate these contradictory findings, a meta-analysis of all available association studies between the G196A polymorphism and the risk of developing PD was conducted. Four out of six identified studies included populations of East Asian descent, and two included populations of European descent (Whites). Overall, the meta-analysis of the allele contrast (A vs G) suggested large heterogeneity between studies (P=0.07, I2 =51%) and no association between G196A and the risk of developing PD: random effects odds ratio (OR)=1.00 [95% CI (0.85, 1.18)]. The sensitivity analysis (exclusion of two studies: one East Asian and one White) with the controls not in Hardy-Weinberg equilibrium showed large heterogeneity (P=0.10, I2 =52%) and no significant association: random effects OR=0.94 [95% CI (0.77, 1.15)]. The subgroup analyses for East Asians and Whites produced no significant association. In addition, the contrast of homozygotes, and the dominant and recessive models for allele A did not support a major role for this polymorphism in the pathogenesis of PD. There were no sources of bias in the selected studies, and the differential magnitude of effect in large vs small studies was not significant. The meta-analysis results suggest that the involvement of the BDNF gene in susceptibility to PD merits further exploration with larger and more rigorous population association studies.
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PMID:The role of G196A polymorphism in the brain-derived neurotrophic factor gene in the cause of Parkinson's disease: a meta-analysis. 1617 6

Apoptosis and necrosis of neurons induced by glutamate and nitric oxide (NO) are associated with various disorders including hypoxic-ischemic brain injury, Alzheimer's disease and Parkinson's disease. In search of endogenous protective factors that inhibit NO-mediated glutamate neurotoxicity, we found that excitotoxicity is suppressed by certain neurotransmitters such as nicotinic acetylcholine and dopamine and growth factors such as NGF and BDNF. We recently purified and isolated a novel neuroprotective substance, which has been named 'serofendic acid', from a lipophilic fraction of fetal calf serum. Mass spectrometry and NMR spectroscopy revealed the chemical structure of serofendic acid (15-hydroxy-17-methylsulfinylatisan-19-oic acid) as a sulfur-containing atisane-type diterpenoid. Serofendic acid exhibited potent protective actions on cortical neurons against neurotoxicity of a NO donor as well as of glutamate, although it did not show appreciable influences on glutamate receptor-mediated responses in these neurons. Electron spin resonance analysis demonstrated that serofendic acid had no direct scavenging activity on NO radicals but was capable of inhibiting the generation of hydroxyl radicals. These findings suggest that serofendic acid is a low-molecular-weight bioactive factor that promotes survival of CNS neurons, probably through the attenuation of free radical-mediated insults.
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PMID:[Endogenous factors regulating neuronal apoptosis]. 1631 2

In addition to the well-documented mood-stabilizing effects of lithium in manic-depressive illness patients, recent in vitro and in vivo studies in rodents and humans have increasingly implicated that lithium can be used in the treatment of acute brain injuries (e.g., ischemia) and chronic neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, tauopathies, and Huntington's disease). Consistent with this novel view, substantial evidences suggest that depressive illness is not a mere neurochemical disease, but is linked to gray matter atrophy due to the reduced number/size of neurons and glia in brain. Importantly, neurogenesis, that is, birth/maturation of functional new neurons, continues to occur throughout the lifetime in human adult brains (e.g., hippocampus); the neurogenesis is impaired by multiple not-fully defined factors (e.g., aging, chronic stress-induced increase of glucocorticoids, and excitotoxicity), accounting for brain atrophy in patients with depressive illness and neurodegenerative diseases. Chronic treatment of lithium, in agreement with the delayed-onset of mood-stabilizing effects of lithium, up-regulates cell survival molecules (e.g., Bcl-2, cyclic AMP-responsive element binding protein, brain-derived neurotrophic factor, Grp78, Hsp70, and beta-catenin), while down-regulating pro-apoptotic activities (e.g., excitotoxicity, p53, Bax, caspase, cytochrome c release, beta-amyloid peptide production, and tau hyperphosphorylation), thus preventing or even reversing neuronal cell death and neurogenesis retardation.
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PMID:Lithium: potential therapeutics against acute brain injuries and chronic neurodegenerative diseases. 1634 Jan 57

The brain-derived neurotrophic factor (BDNF) promotes survival, differentiation and maintenance of neurons in the central nervous system. BDNF 196 G>A and 270 C>T polymorphisms have previously been associated with Alzheimer's disease (AD) and with Parkinson's disease (PD). To study the role of BDNF 196 G>A and 270 C>T polymorphisms in Finnish AD and PD patients we genotyped BDNF 196 G>A and 270 C>T polymorphisms in 97 sporadic AD patients, 52 PD patients and 101 control subjects with polymerase chain reaction. No associations were found between the genotypes studied and AD or PD in Finnish patients. Moreover, no interaction between either BDNF polymorphism and the epsilon 4 allele of apolipoprotein E was found. In conclusion, it seems that the BDNF gene does not contribute significantly to the risk of AD or PD in Finnish patients.
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PMID:No association between the brain-derived neurotrophic factor 196 G>A or 270 C>T polymorphisms and Alzheimer's or Parkinson's disease. 1656 26


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