Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study was undertaken to detect the characteristics of autonomic nervous system disorders in patients with psoriasis concurrent with chronic opisthorchiasis and, on their basis, to develop therapeutic manipulations. Examinations were made in 150 patients with psoriasis concurrent with chronic opisthorchiasis, 100 psoriatic patients without helminthiasis, 100 patients with chronic opisthorchiasis, and 30 healthy individuals. The questionnaire method developed and recommended for use by the All-Union Center of Autonomic Nervous System Diseases was employed for the screening diagnosis of vegetative dystonia syndrome and for the estimation of its severity. The vegetative dystonia syndrome was observed in all patients with psoriasis concurrent with chronic opisthorchiasis. There was an association of the vegetative dystonia syndrome with the area of skin involvement, the severity of psoriasis, the duration of the latter and opisthorchiasis.
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PMID:[Clinical analysis of autonomic nervous system disorders in patients with psoriasis concurrent with chronic opisthorchiasis]. 1656 41

A subgroup of the AAA+ proteins that reside in the endoplasmic reticulum and the nuclear envelope including human torsinA, a protein mutated in hereditary dystonia, is called the torsin family of AAA+ proteins. A multiple-sequence alignment of this family with Hsp100 proteins of known structure reveals a conserved cysteine in the C-terminus of torsin proteins within the Sensor-II motif. A structural model predicts this cysteine to be a part of an intramolecular disulfide bond, suggesting that it may function as a redox sensor to regulate ATPase activity. In vitro experiments with OOC-5, a torsinA homolog from Caenorhabditis elegans, demonstrate that redox changes that reduce this disulfide bond affect the binding of ATP and ADP and cause an attendant local conformational change detected by limited proteolysis. Transgenic worms expressing an ooc-5 gene with cysteine-to-serine mutations that disrupt the disulfide bond have a very low embryo hatch rate compared with wild-type controls, indicating these two cysteines are essential for OOC-5 function. We propose that the Sensor-II in torsin family proteins is a redox-regulated sensor. This regulatory mechanism may be central to the function of OOC-5 and human torsinA.
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PMID:The torsin-family AAA+ protein OOC-5 contains a critical disulfide adjacent to Sensor-II that couples redox state to nucleotide binding. 1855 Jul 99

Dystonia is a neurological disorder characterized by abnormal involuntary movements that are prolonged and often cause twisting and turning. Several genetically modified worms, fruit flies, and rodents have been generated as models of genetic dystonias, in particular DYT1, DYT11, and DYT12 dystonias. Although these models do not show overt dystonic symptoms, the rodent models exhibit motor deficits in specialized behavioral tasks, such as the rotarod and beam-walking tests. For example, in a rodent model of DYT12 dystonia, which is generally stress triggered, motor deficits are observed only after the animal is stressed. Moreover, in a rodent model of DYT1 dystonia, the motor and electrophysiological deficits can be rescued by trihexyphenidyl, a common anticholinergic medication used to treat dystonic symptoms in human patients. Biochemically, the DYT1 and DYT11 animal models also share some similarities to patients, such as a reduction in striatal D2 dopamine receptor and binding activities. In addition, conditional knockout mouse models for DYT1 and DYT11 dystonia demonstrate that loss of the causal dystonia-related proteins in the striatum leads to motor deficits. Interestingly, loss of the DYT1 dystonia causal protein in Purkinje cells shows an improvement in motor performance, suggesting that gene therapy targeting of the cerebellum or intervention in its downstream pathways may be useful. Finally, recent studies using DYT1 dystonia worm and mouse models led to a potential novel therapeutic agent, which is currently undergoing clinical trials. These results indicate that genetic animal models are powerful tools to elucidate the pathophysiology and to further develop new therapeutics for dystonia.
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PMID:Engineering animal models of dystonia. 2389 55