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)

Trinucleotide repeat (TNR) expansion in the gene for TATA binding protein (TBP) has recently been described as causal for spinocerebellar ataxia type 17. The normal number of repeats has been considered to be 42 or less. An intermediate range with reduced penetrance has been assumed to be 43-47 CAA/CAG repeats. We examined this gene in 30 patients with autosomal-dominant cerebellar ataxia (ADCA), 35 patients with sporadic ataxia, 11 patients with Huntington's disease (HD), 351 patients with idiopathic Parkinson's disease (PD), 105 patients with Alzheimer's disease (AD), and 291 controls with no history of neurodegenerative disease. Three patients (one with sporadic PD and two with AD) carrying more than 42 TNRs in the TBP gene were identified. This reveals that the phenotype associated with CAG/CAA expansion in the TBP gene may be heterogeneous.
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PMID:Analysis of polyglutamine-coding repeats in the TATA-binding protein in different neurodegenerative diseases. 1536 89

The presence of late-onset neurological symptoms in male carriers of premutation expansions of the fragile X mental retardation 1 (FMR1) gene has been described recently. One of the clinical symptoms in this fragile X-associated tremor/ataxia syndrome (FXTAS) is parkinsonism. To test the possible association between expanded FMR1 alleles and Parkinson's disease (PD), we determined the size of the FMR1 CGG repeat in 414 male cases of clinically diagnosed parkinsonism, the majority of whom had PD. None of our patients had expanded FMR1 repeats within the premutation range (55-200 CGG repeats). Five patients (1.2%) carry intermediate-size alleles (41-54 CGG repeats). Expansions within the FMR1 gene are not associated with PD in our study.
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PMID:Parkinsonism, FXTAS, and FMR1 premutations. 1539 Jan 27

We aimed to develop and validate a novel rating scale for multiple system atrophy (Unified Multiple System Atrophy Rating Scale-UMSARS). The scale comprises the following components: Part I, historical, 12 items; Part II, motor examination, 14 items; Part III, autonomic examination; and Part IV, global disability scale. For validation purposes, 40 MSA patients were assessed in four centers by 4 raters per center (2 senior and 2 junior raters). The raters applied the UMSARS, as well as a range of other scales, including the Unified Parkinson's Disease Rating Scale (UPDRS) and the International Cooperative Ataxia Rating Scale (ICARS). Internal consistency was high for both UMSARS-I (Crohnbach's alpha = 0.84) and UMSARS-II (Crohnbach's alpha = 0.90) sections. The interrater reliability of most of the UMSARS-I and -II items as well as of total UMSARS-I and -II subscores was substantial (k(w) = 0.6-0.8) to excellent (k(w) > 0.8). UMSARS-II correlated well with UPDRS-III and ICARS (rs > 0.8). Depending on the degree of the patient's disability, completion of the entire UMSARS took 30 to 45 minutes. Based on our findings, the UMSARS appears to be a multidimensional, reliable, and valid scale for semiquantitative clinical assessments of MSA patients.
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PMID:Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS). 1545 68

A neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), occurs in some older men carrying a small CGG repeat expansion (pre-mutation) in the FMR1 gene. We surveyed a sample of older pre-mutation males to estimate the prevalence and spectrum of neurological involvement. Twelve pre-mutation males aged 50-82 years and 11 age-matched normal controls ascertained in an unbiased manner were included in a neurological assessment that also used standard scales for tremor (Clinical Rating Scale for Tremor), ataxia (International Cooperative Ataxia Rating Scale, ICARS) and parkinsonian signs (Unified Parkinson's Disease Rating Scale). Axial FLAIR images of the brain, and neuropsychological and molecular tests were also conducted in pre-mutation carriers. The neurological disorder meeting all the criteria for diagnosis of 'definite' to 'possible' FXTAS occurred in five of 12 pre-mutation carriers (41.7%), and this prevalence was significantly higher compared with normal controls (0%). The ataxia (ICARS) score and the sum of all three tremor/ataxia scores were significantly higher in pre-mutation carriers than in controls, and mRNA was elevated in all but one carrier, but did not correlate with the degree of neurological involvement. In conclusion, the findings provide further evidence that the pre-mutation allele of FMR1 is a significant cause of late-onset neurodegeneration, presenting with a broad spectrum of clinical manifestations.
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PMID:Evidence for, and a spectrum of, neurological involvement in carriers of the fragile X pre-mutation: FXTAS and beyond. 1581 Oct 8

Complexins are presynaptic proteins that bind to the SNARE complex where they modulate neurotransmitter release. A number of studies report changes in complexins in psychiatric (schizophrenia and depression) and neurodegenerative disorders (Huntington's disease, Wernicke's encephalopathy and Parkinson's disease). Here, we characterize the behavioural phenotype of Cplx1 knockout (Cplx1-/-) mice. Cplx1-/- mice develop a strong ataxia in the absence of cerebellar degeneration. Although originally reported to die within 2-4 months after birth, when reared using an enhanced feeding regime, these mice survive normally (i.e. >2 years). Cplx1-/- mice show pronounced deficits in motor coordination and locomotion including abnormal gait, inability to run or swim, impaired rotarod performance, reduced neuromuscular strength, dystonia and resting tremor. Although the abnormal motor phenotype dominates their overt symptoms, Cplx1-/- mice also show other behavioural deficits, particularly in complex behaviours. They have deficits in grooming and rearing behaviour and show reduced exploration in several different paradigms. They also show deficits in tasks reflecting emotional reactivity. They fail to habituate to confinement and show a 'panic' response when exposed to water. The abnormalities seen in the behaviour of Cplx1-/- mice reflect those predicted from the distribution of complexin I in the brain. Our data show that complexin I is essential not only for normal motor function in mice, but also for normal performance of other complex behaviours. These results support the idea that altered expression of complexins in disease states may contribute to the symptomatology of disorders in which they are dysregulated.
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PMID:Profound ataxia in complexin I knockout mice masks a complex phenotype that includes exploratory and habituation deficits. 1600 Mar 19

Supervised learning of different postural tasks in patients with lesions of the motor cortex or pyramidal system (poststroke hemiparesis: 20 patients), nigro-striatal system (Parkinson's disease: 33 patients) and cerebellum (spinocerebellar ataxia: 37 patients) was studied. A control group consisted of 13 healthy subjects. The subjects stood on a force platform and were trained to change the position of the center of pressure (CP) presented as a cursor on a monitor screen in front of the patient. Subjects were instructed to align the CP with the target and then move the target by shifting the CP in the indicated direction. Two different tasks were used. In "Balls", the target (a ball) position varied randomly, so the subject learned a general strategy of voluntary CP control. In "Bricks", the subject had to always move the target in a single direction (downward) from the top to the bottom of the screen, so that a precise postural coordination had to be learned. The training consisted of 10 sessions for each task. The number of correctly performed trials for a session (2 min for each task) was scored. The voluntary control of the CP position was initially impaired in all groups of patients in both tasks. In "Balls", there were no differences between the groups of the patients on the first day. The learning course was somewhat better in hemiparetic patients than in the other groups. In "Bricks", the initial deficit was greater in the groups of parkinsonian and cerebellar patients than in hemiparetic patients. However, learning was more efficient in parkinsonian than in hemiparetic and cerebellar patients. After 10 days of training, the hemiparetic and cerebellar patients completed the acquisition at a certain level whereas the parkinsonian patients showed the ability for further improvement. The results suggest that motor cortex, cerebellum, and basal ganglia are involved in voluntary control of posture and learning different postural tasks. However, these structures play different roles in postural control and learning: basal ganglia are mainly involved in learning a general strategy of CP control while the function of the motor cortex chiefly concerns learning a specific CP trajectory. The cerebellum is involved in both kinds of learning.
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PMID:Supervised learning of postural tasks in patients with poststroke hemiparesis, Parkinson's disease or cerebellar ataxia. 1617 60

The North American Multiple System Atrophy Study Group involves investigators in 12 US medical centers funded by a grant from the National Institutes of Health. The objectives are to examine the environmental and genetic risk factors for MSA; elucidate pathogenic mechanisms underlying the disorder; and refine evaluations used for assessment. During its first year, the group enrolled 87 patients, implemented four cores, and initiated four scientific projects. Most patients among the 87 had parkinsonian features, which frequently began asymmetrically and remained asymmetrical; one-third responded to levodopa and many developed levodopa complications; almost two-thirds of the patients had cerebellar dysfunction, of these 90% had ataxia; urinary incontinence occurred commonly, and sleep disorders affected most. The investigators studied the effects of oxidative and nitrative stress upon the formation of alpha-synuclein inclusions; generated transgenic models of alpha-synuclein accumulation that recapitulate several behavioral and neuropathological features of MSA; and compared the severity of the autonomic features of MSA, Parkinson's disease and dementia with Lewy bodies.
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PMID:The North American Multiple System Atrophy Study Group. 1628 10

Western medicine was introduced to Taiwan in 1865 when Dr. James L. Maxwell, a missionary doctor of the English Presbyterian Church, established a hospital in nowadays Tainan. The period of the missionary medicine lasted for over 30 years until Japanese took over. During this period, however, official records of diseases in Taiwan that were based on Western medicine were scanty or not available. Fortunately, port surgeons stationing respectively in Tamsui and Kelung in the north and in Takow and Taiwan-fu in the south reported semi-annually diseases seen in the ports, foreign communities and missionary hospitals that they volunteered to work. The diseases reported by port surgeons were either cases or summary of cases with classification and statistics. Their medical reports covered from 1871 to 1900. The data show that neurological diseases and/or disorders in the late 19th century Taiwan were uncommon, comprising only 2-3% of total diseases. The data further show that common neurological diseases were leprosy, opium smoking, syphilitic dementia (GPI), paralysis, hysteria, neuralgia, epilepsy, mania, sciatica, meningitis and ataxia. Stroke was uncommon while Parkinson's disease and Alzheimer's disease were not mentioned, indicating that neurological diseases related to old age and neurodegeneration were not yet a threat to health. Similarly, headache, insomnia, anxiety and depression, hallmark of functional disorders of the modern society, were also not mentioned, suggesting that these disorders were indeed rare or did not cause sufficient concern for patients to seek help from doctors of Western medicine.
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PMID:[Neurological diseases in late 19th century Taiwan--medical reports of the Chinese Imperial Maritime Customs]. 1642 51

Here, we propose a novel hypothesis that 14-3-3 zeta might act as a sweeper of misfolded proteins by facilitating the formation of aggregates, which are referred to as inclusion bodies. Studies on the localization of the 14-3-3 proteins in different types of inclusion bodies in the brain including neurofibrillary tangle in Alzheimer's disease, pick bodies in Pick's disease, Lewy body-like hyaline inclusions in sporadic amyotrophic lateral sclerosis, prion/florid plaques in sporadic/variant Creutzfeldt-Jakob disease, nuclear inclusions in spinocerebellar ataxia-1, and possibly Lewy bodies in Parkinson's disease suggest a close association of these diseases with 14-3-3 zeta. The highly conserved hydrophobic surface of the amphipathic groove in 14-3-3 zeta represents a general mechanism with diverse cellular proteins, and it may also allow for the molecular recognition of misfolded proteins by hydrophobic interaction in disease conditions. When the abnormal processing of misfolded proteins overwhelms the quality control systems of the cell, it is likely that 14-3-3 zeta is recruited to form deposits of protein aggregates with nonnative, misfolded proteins in order to protect the cell against toxicity. Hence, 14-3-3 zeta may be considered as an auxiliary therapeutic tool in the protein aggregation disorders.
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PMID:The alternative role of 14-3-3 zeta as a sweeper of misfolded proteins in disease conditions. 1651 99

Recent reports of SCA2 and SCA3 patients who presented with levodopa responsive parkinsonism have generated considerable interest as they have implications for genetic testing. It is unclear whether ethnic race alone or founder effects within certain geographical region explain such an association. In this study, we conducted genetic analysis of SCA2, 3, 17 in an ethnic Chinese cohort with early onset and familial Parkinson's disease (PD) and healthy controls. A total of 191 subjects comprising of 91 PD and 100 healthy controls were examined. We identified one positive case of SCA2 in an early-onset sporadic PD patient who had CAG 36 repeats, yielding a prevalence of 2.2% in early-onset sporadic PD patients and less than 1.0% in our study PD population. The size of the repeats was lower than the expanded repeats (38-57) in SCA2 patients with ataxia in our population. All the children of the patient were physically normal even though some of them carried the repeat expansion of similar size. No cases and controls were positive for SCA3 and SCA17. We do not think routine screening of SCA2, SCA3 and SCA17 for all idiopathic PD patients is cost-effective in our ethnic Chinese population. However, SCA2 should be a differential diagnosis in young onset sporadic PD when genetic mutations of other known PD genes have been excluded.
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PMID:Genetic analysis of SCA2, 3 and 17 in idiopathic Parkinson's disease. 1668 13


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