Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new engineering strain, Bacillus pumilus c172-14 (pBX 96), was obtained by introducing the pBX 96 plasmid, which carries the alpha-amylase amy gene, into the host strain of alkalophilic Bacillus pumilus c172 via transformation. The newly constructed strain was found to express the amy gene and could use starch instead of glucose or starch hydrolysate as carbon source for its fermentation of alkaline protease. The pBX 96 plasmid in the new host was found to be segregationally and structurally stable. The expression of amy gene did not affect the host strain's resistance to bacteriophages. Moreover, the level of alkaline protease was improved significantly compared with the parent strain. The constructed strain gave a maximum alkaline protease activity of 14,014 U/ml in shaking flask after 48 h cultivation when growing in a medium containing 6% corn meal, 4% soybean flour, 0.4% Na2HPO4, 0.03% KH2PO4, 0.02% MgCl2, 0.3% CaCl2, 0.25% Na2CO3, 0.1% glucose, and 20 microg/ml kanamycin (pH 7.0). The optimal pH value and temperature of the alkaline protease were 11.0 and 40 degrees C, respectively. This enzyme was stable over a pH range of 8-11. Its residual activity remained at 100% when treated under a temperature of less than 45 degrees C for 30 min. The corresponding residual activity reduced to 65% of its optimal value at 60 degrees C for 30 min. The alkaline protease was a kind of serine protease, which was demonstrated by the complete inactivation by PMSF (1 mM). This newly constructed strain will be useful in the alkaline protease industry.
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PMID:Fermentation of starch for enhanced alkaline protease production by constructing an alkalophilic Bacillus pumilus strain. 1169 13

Recent studies have reported that alleles in the premutation range in the FMR1 gene in males result in increased FMR1 mRNA levels and at the same time mildly reduced FMR1 protein levels. Some elderly males with premutations exhibit an unique neurodegenerative syndrome characterized by progressive intention tremor and ataxia. We describe neurohistological, biochemical and molecular studies of the brains of mice with an expanded CGG repeat and report elevated Fmr1 mRNA levels and intranuclear inclusions with ubiquitin, Hsp40 and the 20S catalytic core complex of the proteasome as constituents. An increase was observed of both the number and the size of the inclusions during the course of life, which correlates with the progressive character of the cerebellar tremor/ataxia syndrome in humans. The observations in expanded-repeat mice support a direct role of the Fmr1 gene, by either CGG expansion per se or by mRNA level, in the formation of the inclusions and suggest a correlation between the presence of intranuclear inclusions in distinct regions of the brain and the clinical features in symptomatic premutation carriers. This mouse model will facilitate the possibilities to perform studies at the molecular level from onset of symptoms until the final stage of the disease.
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PMID:The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome. 1270 Jan 64

Environmental toxins have been implicated in the etiology of Parkinson's disease. Recent findings of defects in the ubiquitin-proteasome system in hereditary and sporadic forms of the illness suggest that environmental proteasome inhibitors are candidate PD-inducing toxins. Here, we systemically injected six doses of naturally occurring (epoxomicin) or synthetic (Z-lle-Glu(OtBu)-Ala-Leu-al [PSI]) proteasome inhibitors into adult rats over a period of 2 weeks. After a latency of 1 to 2 weeks, animals developed progressive parkinsonism with bradykinesia, rigidity, tremor, and an abnormal posture, which improved with apomorphine treatment. Positron emission tomography demonstrated reduced carbon-11-labeled 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT) binding to dopaminergic nerve terminals in the striatum, indicative of degeneration of the nigrostriatal pathway. Postmortem analyses showed striatal dopamine depletion and dopaminergic cell death with apoptosis and inflammation in the substantia nigra pars compacta. In addition, neurodegeneration occurred in the locus coeruleus, dorsal motor nucleus of the vagus, and the nucleus basalis of Meynert. At neurodegenerative sites, intracytoplasmic, eosinophilic, alpha-synuclein/ubiquitin-containing, inclusions resembling Lewy bodies were present in some of the remaining neurons. This animal model induced by proteasome inhibitors closely recapitulates key features of PD and may be valuable in studying etiopathogenic mechanisms and putative neuroprotective therapies for the illness.
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PMID:Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease. 1686 91

We report a review on progress in the etiology and pathogenesis of Parkinson's disease (PD). We also report the long-term prognosis of PD patients seen in our clinic. Modern research on the pathogenesis started after the discovery of MPTP. We found inhibition of mitochondrial complex I by MPTP and MPP+. Mitochondrial respiratory failure induces oxidative damage to high molecular weight substances. Both mitochondrial failure and oxidative stress are important triggers of apoptosis. We found TUNEL positive nigral neurons in PD patients suggesting involvement of apoptosis in the pathogenesis. Interaction of genetic risk factors and environmental neurotoxins has been implicated in the etiology of PD. While we were investigating MnSOD gene polymorphism in PD patients, we found a young onset autosomal recessive PD family that was linked to the MnSOD locus. Subsequent linkage analysis on 13 families of young onset autosomal recessive families disclosed the linkage of this disease to the telomeric region of the long arm of chromosome 6 (6q25.2-27). Then we were lucky enough to find a patient who had a deletion of one of the microsatellite markers (D6S305) that we were using in the linkage analysis. We thought this marker might be located within the disease gene and this was the case. We screened the Keio BAC library with this marker, and eventually we cloned a novel gene encompassing 1.4 Mb; we named it parkin. The coding region consisted of 1,395 base pairs. The parkin protein had an unique sequence in that there was a 30% homology in the amino terminal region and two RING-finger motives on the carboxy terminal side. This unique structure suggested that the parkin protein was related to the ubiquitin-proteasome system. Parkin protein turned out to be an ubiquitin-protein ligase. Numbers of parkin-interacting proteins were reported in the literature and accumulation of parkin-substrates is likely to be the cause for the nigral neuronal death in this familial PD. Regarding the prognosis of PD, we analyzed the patients who visited our clinic from January 1, 1989 to December 31, 2002. The total of patients recruited was 1,772. The average age of onset was 57.2 years. Mean levodopa dose at the final examination was 479 mg/day. The most common initial symptom was tremor which was seen in 51% of the patients. Total percentage of patients who had tremor during the course of the disease was 75%. Long-term prognosis was evaluated on a subgroup of the patients who visited our clinic within 5 years from the onset and Hoehn and Yahr stage III or less when first seen. Analysis was done by the Kaplan-Meier survival curve. Percentages of patients who reached Hoehn and Yahr III 5, 10, and 15 years after the onset were 24%, 46%, and 65%, respectively. Percentages of patients who developed wearing off fluctuations were 5, 10, and 15 years after the start of levodopa were 18%, 46%, and 55%, respectively. Overall mortality on the total investigated patients was 7.9%. When compared to the age at death of Japanese population, mortality of men PD patients became very close to that of the general population in the year 2003. However, that in women PD patients showed significantly shorter survival compared to Japanese female population. Average ages of onset and the death were essentially similar between men and women PD patients. Survival curves to reach stage III and wearing off showed slightly but significantly faster time courses for women compared to those of men. This was an unexpected observation and its mechanism was discussed. It is our conclusion that overall prognosis of PD patients is improving and both patients and treating physicians should take an optimistic attitude to the disease.
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PMID:[Progress in the basic and clinical aspects of Parkinson's disease]. 1565 Dec 81

In this work, we have investigated the role of the sperm proteasome during in vitro fertilization (IVF) and gamete interaction in the mouse. Proteasome activity was measured in extract and intact sperm using a specific substrate. In addition, sperm were treated with specific proteasome inhibitors and evaluated during IVF, binding to the zona pellucida, and progesterone- and zona pellucida-induced acrosome reactions. In other experiments, sperm membrane proteins were obtained resuspending them in Triton X-114, shaking vigorously and let standing by 4 hr. Soluble sperm proteins were partitioned in the aqueous phase and sperm membrane proteins in the detergent phase. In both phases, proteasome activity was measured. Labeling of cell surface sperm proteins was carried out with the cell-impermeable NHS-LC biotin, extracted with Triton X-114, and mixing with avidin-agarose beads. Nonpermeabilized sperm were incubated with an anti-proteasome monoclonal antibody and evaluated by indirect immunofluorescence. The results indicate that sperm extracts as well as intact sperm had proteasome activity; the sperm proteasome was involved in IVF, specifically during sperm-zona pellucida binding and the acrosome reaction; soluble sperm membrane proteins exhibited proteasome activity; biotin experiments indicated the presence of proteasomes on the sperm surface, which was corroborated by indirect immunofluorescence experiments. All these observations indicate that the mouse sperm proteasome participates in the binding to the zona pellucida and the acrosome reaction and that there is a pool of proteasomes located on the sperm head.
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PMID:Role of the sperm proteasome during fertilization and gamete interaction in the mouse. 1579 92

Comparative studies of enzymatic synthesis of glucose esters under ultrasound and shaking were carried out in nonaqueous media. The influence of solvents, enzymes, chain length of the acyl donors, the power of the ultrasound bath, and intermittent ultrasound on the enzymatic synthesis was investigated. Among the eight solvents selected, pyridine was the most appropriate with alkaline protease from Bacillus subtilis whether under ultrasound or shaking. The acceleration effect of ultrasound with Novozym 435 and the alkaline protease from B. subtilis-catalyzed transesterification increased with the chain length of acyl donors, decreasing from C(10) to C(4). We also investigated the influence of the power (50, 100, and 120 W) of the ultrasound irradiation and the manner of operation (continuous ultrasound, 10 min ultrasound/20 min shaking without ultrasound) on the transesterification. The results showed that higher power and continual operational gave the better acceleration. Ultrasound did not change the character and selectivity of the enzyme in the transesterification.
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PMID:Ultrasound-accelerated enzymatic synthesis of sugar esters in nonaqueous solvents. 1604 20

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder with core features of action tremor and cerebellar gait ataxia. Frequent associated findings include parkinsonism, executive function deficits and dementia, neuropathy, and dysautonomia. Magnetic Resonance Imaging studies in FXTAS demonstrate increased T2 signal intensity in the middle cerebellar peduncles (MCP sign) in the majority of patients. Similar signal alterations are seen in deep and subependymal cerebral white matter, as is general cortical and subcortical atrophy. The major neuropathological feature of FXTAS is the presence of intranuclear, neuronal, and astrocytic, inclusions in broad distribution throughout the brain and brainstem. FXTAS is caused by moderate expansions (55-200 repeats; premutation range) of a CGG trinucleotide in the fragile X mental retardation 1 (FMR1) gene, the same gene which causes fragile X syndrome when in the full mutation range (200 or greater CGG repeats). The pathogenic mechanism is related to overexpression and toxicity of the FMR1 mRNA per se. Although only recently discovered, and hence currently under-diagnosed, FXTAS is likely to be one of the most common single-gene disorders leading to neurodegeneration in males. In this report, we review information available on the clinical, radiological, and pathological features, and prevalence and management of FXTAS. We also provide guidelines for the practitioner to assist with identifying appropriate patients for DNA testing for FXTAS, as well as recommendations for genetic counseling once a diagnosis of FXTAS is made.
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PMID:Fragile X-associated tremor/ataxia syndrome: clinical features, genetics, and testing guidelines. 1761 23

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by rigidity, bradykinesia, postural instability and resting tremor. The major symptoms are related to the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. The recent discovery of PARK genes causing familial forms of PD has led to a new approach in the study of the disease. The cause and pathogenesis of PD remains unknown; mitochondrial dysfunction, oxidative damage, endoplasmic reticulum stress, failure of the ubiquitin-proteasome system, environmental factors and genetic predisposition might all be involved. Toxin-induced PD animal models and genetic mouse models that mimic familial PD have contributed to investigating the molecular pathogenesis and treatment of the disease. Recently, neurogenesis in the striatum and subventricular zones in PD animal models have been reported. This review discusses molecular pathogenesis, experimental disease models and recent cell-based therapeutic approaches for PD.
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PMID:Molecular pathogenesis, experimental models and new therapeutic strategies for Parkinson's disease. 1763 51

Fragile X-associated tremor/ataxia (FXTAS) is a late onset disorder caused by a premutation in the FMR1 gene, in which neurological symptoms are associated with white matter (wm) changes, especially within the middle cerebellar peduncles (MCP sign), seen on magnetic resonance images (MRIs). We report a discrepancy between obvious radiological presentations and minimal clinical involvement in two younger male premutation carriers. These carriers, aged 52 and 39 years, showed distinct MCP sign, but reported no neurological symptoms. If this discrepancy represents the initial stage of FXTAS, our findings suggest the possibility of early diagnosis from MRI scans.
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PMID:A low symptomatic form of neurodegeneration in younger carriers of the FMR1 premutation, manifesting typical radiological changes. 1805 83

Parkinson's disease is a neurodegenerative condition characterized by tremor, rigidity, bradykinesia, and postural instability. Smoking is an inverse risk factor for Parkinson's disease, although the mechanism for this apparent neuroprotection is not definitively established. Smoking consistently upregulates nicotinic acetylcholine receptor levels in various brain regions known to be involved in Parkinson's disease. The ubiquitin-proteasome system--the system that tags and removes unwanted, misfolded, or damaged proteins from cells--regulates nicotinic receptor levels. The ubiquitin-proteasome system has also been implicated in Parkinson's disease, with aberrant activity identified in both sporadic and familial forms of the disease. The involvement of the ubiquitin-proteasome system in nicotinic receptor regulation and Parkinson's disease pathology suggests a link between the two, which forms the basis of the present hypothesis. Specifically, this paper considers the hypothesis that smoking reduces the risk of Parkinson's disease through the upregulation of nicotinic cholinergic receptors in key brain regions involved in Parkinson's disease. This receptor upregulation is hypothesized to increase activity of the ubiquitin-proteasome system, which is believed to prevent neurodegeneration caused by the accumulation of misfolded or damaged proteins or other consequences of inadequate protein sequestration and/or degradation. This hypothesis is supported by evidence documenting the upregulation of nicotinic receptors in the brains of smokers, neuroprotective effects of nicotine, reduced activity of the ubiquitin-proteasome in Parkinson's disease, and increased activity of the ubiquitin-proteasome system in animals exposed to chronic nicotine. Additional research is needed to test several predictions of the hypothesis, including increased activity of the ubiquitin-proteasome system in key brain regions of smokers.
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PMID:Does smoking reduce the risk of Parkinson's disease through stimulation of the ubiquitin-proteasome system? 1954 50


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