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)

Parkinson's disease (PD) is a progressive disease that usually affects the motor system but is also associated with a non-motor symptom (NMS) complex that ranges from dribbling saliva, constipation, depression, sleep disorders, apathy, hallucinations, and dementia. These features contribute significantly to morbidity and institutionalization, more than quadrupling the cost of care. Furthermore, recent evidence suggests that NMS such as constipation, olfaction, rapid eye movement behavior disorder, fatigue, and depression may be markers of a preclinical stage of PD. PD-NMS are not well recognized in clinical practice and part of the reason is the lack of any instrument that aims to assess the complex range of NMS of PD in a unified and integrated manner. Recently, an international, multidisciplinary PD-NMS group has developed an integrated questionnaire and scale to assess NMS of PD in a comprehensive manner. This will help improve care and treatment of PD in the future.
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PMID:The non-motor symptom complex of Parkinson's disease: a comprehensive assessment is essential. 1598 11

PD (Parkinson's disease) is an aetiologically heterogeneous disorder characterized by a clinical phenotype consisting of resting tremor, rigidity and bradykinesia. Motor symptoms are associated with a progressive loss of dopaminergic neurons, with Lewy body inclusions within surviving neurons. Although heritability studies have shown evidence of familial aggregation, twin studies have provided limited support for a genetic aetiology. Nevertheless, classical linkage methods have nominated 11 regions of the genome and pathogenic mutations have been identified in several genes, including alpha-synuclein, parkin, ubiquitin C-terminal hydrolase L1, oncogene DJ-1, PTEN-induced protein kinase 1 and microtubule-associated protein tau. Most recently, heterozygous mutations in LRRK2 (leucine-rich repeat kinase 2) were found to cause late-onset, autosomal-dominant PD. Despite their consistent clinical phenotype, family members with LRRK2 mutations can have variable alpha-synuclein and tau pathologies. Lrrk2 is a member of the Roc (Ras of complex proteins) family, with Ras GTPase and MAPKKK (mitogen-activated protein kinase kinase kinase) catalytic domains. Thus its discovery highlights vesicle dynamics and secondary-messenger signalling in disease pathophysiology. To diagnose a disease accurately and effectively treat it, requires an understanding of its molecular pathogenesis. Herein, we provide an overview of the genetics of PD, how these discoveries are revolutionizing long-held beliefs and more importantly how this knowledge may be translated into patient therapy.
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PMID:Pathophysiology, pleiotrophy and paradigm shifts: genetic lessons from Parkinson's disease. 1604 50

The mental rotation of objects requires visuospatial functions mediated by the parietal lobes, whereas the mental rotation of hands also engages frontal motor-system processes. Nondemented patients with Parkinson's disease (PD), a frontostriatal disorder, were predicted to be impaired on mentally rotating hands. Side of PD motor symptom onset was investigated because the left motor cortices likely have a causal role in hand mental rotation. The prediction was that patients with right-side onset (RPD, greater left-hemisphere dysfunction) would commit more errors rotating hands than patients with left-side onset (LPD). Fifteen LPD, 12 RPD, and 13 normal control adults (NC) made same/different judgments about pairs of rotated objects or hands. There were no group differences with objects. When rotating hands, RPD, but not LPD, made more errors than the NC group. A control experiment evaluated whether visual field of presentation explained differences between PD subgroups. In the first experiment (1A), the hand to be mentally rotated was presented in the right visual field, but here (1B) it was presented in the left visual field. Only the LPD group made more errors than the NC group. The evidence suggests a double dissociation for the RPD and LPD groups between tasks differing in visual-field presentation. The findings indicate that hemifield location of a to-be-rotated hand stimulus can cause the hemispheric frontoparietal networks to be differentially engaged. Moreover, frontostriatal motor systems and the parietal lobes play a necessary role during the mental rotation of hands, which requires integrating visuospatial cognition with motor imagery.
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PMID:Frontostriatal circuits are necessary for visuomotor transformation: mental rotation in Parkinson's disease. 1606 Dec 63

Parkinson's disease (PD) is a basal ganglia disorder. Motor symptoms develop insidiously following substantial neurodegeneration of the dopamine (DA) neurons in the nigrostriatal system and produce slowed, infrequent movements, postural instability, and gait changes. A thorough understanding of neurochemical compensations occurring in the striatum during early stages of PD is crucial in identifying components that are altered initially as the DA is depleted. Producing an incomplete lesion of the nigrostriatal DA system in rats would mimic the principal early neurochemical features of human PD. We infused 6-hydroxydopamine unilaterally into the substantia nigra to reach a target of approximately 50% depletion in striatal DA at 4 weeks. This was evaluated by HPLC analysis of tissue DA content and monitored behaviorally by forepaw use reflecting asymmetries in striatal DA levels. DA loss was assessed by using tyrosine hydroxylase immunohistochemical staining, and the data were conjoined with the behavioral assessments. We found that activated caspase-3, its actin cleavage product fractin, and components of the apoptosome were increased significantly in DA-depleted striatum. Thus mobilization of the intrinsic programmed cell death pathway occurred, without cell loss. Elevations in apoptogenic proteins were pronounced in enkephalinergic striatopallidal neurons compared with the substance P-containing striatonigral neurons. Our findings suggest that cellular homeostatic imbalances that accompany even mild striatal DA depletion take time to develop, differentially affect the striatal output pathways, and may be an important feature of early-stage PD. These observations could be capitalized upon to develop therapeutic interventions in the preclinical phases of the disorder.
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PMID:Partial dopamine loss enhances activated caspase-3 activity: differential outcomes in striatal projection systems. 1618 Feb 25

The short plasma half-life limits the antiparkinsonian efficacy of levodopa/carbidopa (LD/CD). Administration of LD/CD with the catechol-O-methyltransferase inhibitor entacapone in one tablet (LCE) may extend plasma half-life of LD and thus its effect on motor symptoms in patients with Parkinson's disease (PD). The objectives of this study were to monitor the motor response to a switch from LD/CD to LCE by a simultaneous performance of an instrumental motor test and rating of motor symptoms and to compare the LD plasma behavior between both conditions in terms of stability. Twenty-one treated PD patients received LD/CD and then the identical oral LD dosage of LCE within a standardized setting on 2 consecutive days. Rating better reflected the motor improvement after LD application than the instrumental test. Motor symptoms of PD patients decreased significantly more during the LCE than the LD/CD condition, probably due to significantly higher LD plasma levels and a significantly less pronounced fall of the LD concentrations following the second LD intake. Our study shows a more stable LD plasma behavior during LCE intake and accordingly a better effect on motor symptoms according to rating outcomes and motor test results to a lesser extent.
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PMID:Inhibition of catechol-O-methyltransferase contributes to more stable levodopa plasma levels. 1621 93

It is well known that applying vibrations to men influences multiple physiological functions. The authors analysed post effects of whole-body-vibration (WBV) on motor symptoms in Parkinson's disease (PD). Sixty-eight persons with PD were randomly subdivided into one experimental and one control group. Motor symptoms were assessed by the UPDRS (Unified Parkinson's Disease Rating Scale) motor score. A cross-over design was used to control treatment effects. The treatment consisted of 5 series of whole-body-vibration taking 60 seconds each. On average a highly significant (p<0.01) improvement of 16.8% in the UPDRS motor score was found in the treatment group. Only marginal changes (p>0.05) were found in the control group. The cross-over procedure showed comparable treatment effects (14.7% improvement after treatment). With respect to different symptom clusters only small changes were found in limb akinesia and cranial symptoms. By contrast, tremor and rigidity scores were improved by 25% and 24%, respectively. According to the structure of symptom changes it is unlikely that these effects are explainable on peripheral sensory level, exclusively. With respect to the findings of other studies one can speculate about changes in activation of the supplementary motor area and in neurotransmitter functions.
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PMID:The effects of random whole-body-vibration on motor symptoms in Parkinson's disease. 1672 Sep 35

Freezing of gait (FOG) is a disabling episodic gait disturbance that is common among patients with Parkinsonism. FOG typically lasts a few seconds and is associated with a unique sensation: the patient feels that his feet are glued to the ground, causing him to remain in place despite making a concerted effort to overcome the motor block and move forward. Traditionally, FOG has been viewed as a motor symptom of advanced Parkinson's disease. Here we describe evidence which demonstrates that mental conditions also likely play an important role in the pathogenesis of FOG. Stress, anxiety, depression and cognitively challenging situations are associated with FOG, and may set the stage for and increase the likelihood that FOG occurs. A conceptual model that explains how mental conditions may modulate FOG is developed.
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PMID:The role of mental function in the pathogenesis of freezing of gait in Parkinson's disease. 1678 Aug 86

Levodopa (LD) application improves motor symptoms in patients with Parkinson's disease (PD) patients. Little is known on further effects of LD, which induced lower plasma levels of cortisol and lower serotonergic activity in certain brain areas of fish. Objectives of this trial were to analyse levels of cortisol, LD and 3-O-methyldopa (3-OMD) after administration of LD/benserazide in long term treated PD patients. 12 PD patients, taken off their regular treatment for at least 12 hours, received soluble 200 mg LD/50 mg benserazide under stress free conditions. Motor symptoms improved, LD and 3-OMD levels increased, whereas cortisol concentrations started to decrease significantly 30 minutes after LD intake. This reduced cortisol release may result from an overflow of exogenous LD in the brainstem. This hypothetically causes an reduced 5-HT content in neurons projecting to the hypothalamic structures, which are involved in the partial 5-HT dependent central regulation of peripheral cortisol release.
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PMID:Acute levodopa administration reduces cortisol release in patients with Parkinson's disease. 1693 91

The relation of body side of motor symptom onset in Parkinson's disease (PD) to memory measures associated with hemispheric dominance was examined. Fourteen patients with right body side motor symptom onset (RPD, inferred left hemisphere dysfunction) and 16 patients with left side onset (LPD, right hemisphere dysfunction) were administered measures of verbal (Hopkins Verbal Learning Test-Revised) and visual memory (Brief Visual Memory Test-Revised), that require similar task demands and are associated with left or right hemisphere dominance, respectively. The LPD group demonstrated poorer visual than verbal memory, both within group and in comparison to the RPD group. By contrast, the RPD group showed poorer verbal than visual memory within group. These findings suggest that side of motor symptom onset is associated with asymmetrical memory dysfunction.
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PMID:Body side of motor symptom onset in Parkinson's disease is associated with memory performance. 1696 53

It is well known that many patients with Parkinson's disease experience neuropsychological decline. However, the nature and extent of mental status change varies widely, with some patients showing mild or no cognitive impairments and others exhibiting frank dementia. Research has shown that several clinical disease parameters may differentially correlate with patterns of neuropsychological dysfunction. The present study examined side and type of motor symptom at disease onset and their relationship to cognition in idiopathic Parkinson's disease (PD). We identified 58 patients who initially presented with one of the following symptom profiles: right-side tremor onset (RSO-T; n = 15), right-side bradykinesia/rigidity onset (n = 12), left-side tremor onset (n = 19), and left-side bradykinesia/rigidity onset (n = 12). There were no differences between groups in disease duration, overall mental status, education, or depression severity. We administered a battery of neuropsychological measures to the four PD subgroups and a group of matched control subjects (n = 40). MANCOVAs controlling for age revealed patients with RSO-T performed significantly better than the other three PD subgroups across the entire neuropsychological battery. Further, the RSO-T subgroup performed comparably to controls. In contrast, the other three PD subgroups showed widespread cognitive deficits. These findings suggest an intricate relationship between motor symptom and side of disease onset and it is the combination of these factors that may influence the disease course and extent of cognitive deterioration. Furthermore, patients who develop tremor on the right side of their body represent a distinct subgroup of PD patients who exhibit relative sparing of cognitive function.
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PMID:Side and type of motor symptom influence cognition in Parkinson's disease. 1699 Nov 55


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