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 whether striatal alpha(2)-adrenoceptors or N-methyl-d-aspartate (NMDA) receptors influence descending regulation of neuropathic hypersensitivity in the rat by microinjecting an alpha(2)-adrenoceptor agonist or NMDA-receptor antagonist into the dorsal striatum in animals with a spinal nerve ligation-induced neuropathy. Hypersensitivity was assessed in the hind limb by monofilaments and paw pressure test. Various neurotransmitter receptor antagonists were administered into the striatum or intrathecally to determine striatal and spinal neurotransmitters mediating the modulatory influence. The results indicate that the striatum has a dual effect on neuropathic hypersensitivity via two distinct pathways descending to the spinal cord. First, hypersensitivity is reduced following activation of noradrenergic alpha(2)-adrenoceptors and downstream dopamine D2 receptors in the striatum. This antihypersensitivity effect is predominantly ipsilateral and it descends via parallel dopaminergic and serotoninergic pathways to act on spinal dopamine D2 and 5-HT(1A) receptors, respectively. Second, tonic activation of striatal NMDA receptors promotes hypersensitivity by suppressing spinal GABAergic inhibition. The antihypersensitivity actions induced by striatal drug administrations were not associated with motor effects as suggested by lack of effect on the threshold of the uninjured limb or amplitude of the innocuous H-reflex. Involvement of striatal dopamine D2 receptors in the noradrenergic pain inhibitory circuitry may explain why disorders causing hypofunction of the striatal dopaminergic system, such as in Parkinson's disease, have been associated with pain. Furthermore, our findings indicate that striatal NMDA receptors provide a tonic supramedullary drive for medullospinal facilitatory influence that is known to be of importance for neuropathic hypersensitivity.
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PMID:Dual influence of the striatum on neuropathic hypersensitivity. 1787 Feb 40

Restless legs syndrome (RLS) has been described in association with a number of conditions including iron deficiency, neuropathy and Parkinson's disease. Here we report a patient who developed RLS concurrent with the development of classic post-polio syndrome (PPS), 40 years after recovery from an episode of paralytic poliomyelitis. PPS is still frequently encountered in neurological practice, and clinicians should be aware of the possibility of associated RLS.
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PMID:Restless legs may be associated with the post-polio syndrome. 1837 19

Salsolinol, an endogenous neurotoxin, is known to be involved in the neuropathy of Parkinson's disease and chronic alcoholism. In these diseases, increased thrombotic events are also commonly reported, yet the mechanism underlying remains poorly understood. Here we report that salsolinol can enhance agonist-induced platelet aggregation and granular secretion, which is essential in the thrombus formation. In rat and human platelets, agonist-induced platelet aggregation was significantly increased by salsolinol in a concentration-dependent manner. Agonist-induced granular secretions of serotonin and concomitant P-selectin expression were also augmented by salsolinol. alpha2-adrenergic blockers attenuated the salsolinol-enhanced aggregation and the inhibition of cyclic AMP generation was found, suggesting the involvement of alpha2-adrenergic receptor-mediated pathways in these events. In accord with the in-vitro results, in an arterial and venous thrombosis model in vivo in the rat, salsolinol shortened vessel occlusion time and increased thrombus formation, respectively. In conclusion, we demonstrated that salsolinol can enhance agonist-induced aggregation and granular secretion in platelets through alpha2-adrenergic receptor activation, which resulted in the increased thrombus formation in vivo. These results suggest that salsolinol-enhanced platelet aggregation could be a possible contributing factor to the thrombotic events observed in Parkinson's disease and alcoholism.
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PMID:Salsolinol, an endogenous neurotoxin, enhances platelet aggregation and thrombus formation. 1861 38

Restless-legs syndrome (RLS) is a sensorimotor disorder, characterized by an irresistible urge to move the legs usually accompanied or caused by uncomfortable and unpleasant sensations. It begins or worsens during periods of rest or inactivity, is partially or totally relieved by movements and is exacerbated or occurs at night and in the evening. RLS sufferers represent 2 to 3% of the general population in Western countries. Supportive criteria include a family history, the presence of periodic-leg movements (PLM) when awake or asleep and a positive response to dopaminergic treatment. The RLS phenotypes include an early onset form, usually idiopathic with a familial history and a late onset form, usually secondary to peripheral neuropathy. Recently, an atypical RLS phenotype without PLM and l-DOPA resistant has been characterized. RLS can occur in childhood and should be distinguished from attention deficit/hyperactivity disorder, growing pains and sleep complaints in childhood. RLS should be included in the diagnosis of all patients consulting for sleep complaints or discomfort in the lower limbs. It should be differentiated from akathisia, that is, an urge to move the whole body without uncomfortable sensations. Polysomnographic studies and the suggested immobilization test can detect PLM. Furthermore, an l-DOPA challenge has recently been validated to support the diagnosis of RLS. RLS may cause severe-sleep disturbances, poor quality of life, depressive and anxious symptoms and may be a risk factor for cardiovascular disease. In most cases, RLS is idiopathic. It may also be secondary to iron deficiency, end-stage renal disease, pregnancy, peripheral neuropathy and drugs, such as antipsychotics and antidepressants. The small-fiber neuropathy can mimic RLS or even trigger it. RLS is associated with many neurological and sleep disorders including Parkinson's disease, but does not predispose to these diseases. The pathophysiology of RLS includes an altered brain-iron metabolism, a dopaminergic dysfunction, a probable role of pain control systems and a genetic susceptibility with nine loci and three polymorphisms in genes serving developmental functions. RLS treatment begins with the elimination of triggering factors and iron supplementation when deficient. Mild or intermittent RLS is usually treated with low doses of l-DOPA or codeine; the first-line treatment for moderate to severe RLS is dopaminergic agonists (pramipexole, ropinirole, rotigotine). In severe, refractory or neuropathy-associated RLS, antiepileptic (gabapentin, pregabalin) or opioid (oxycodone, tramadol) drugs can be used.
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PMID:[Restless-legs syndrome]. 1865 14

Primary open-angle glaucoma (POAG) is a pressure-sensitive optic neuropathy which results in the death of retinal ganglion cells and causes associated loss of vision. Presently, the only accepted treatment strategy is to lower the intraocular pressure; however, for some patients this is insufficient to prevent progressive disease. Although the pathogenesis of POAG remains unclear, there is considerable evidence that energy failure at the optic nerve head may be involved. Neuroprotection, a strategy which directly enhances the survival of neurons, is desirable, but remains clinically elusive. One particular form of neuroprotection involves the notion of enhancing the energy supply of neurons. These 'bioenergetic' methods of neuroprotection have proven successful in animal models of other neurodegenerative diseases and conditions, including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and traumatic brain injury, but have been relatively unexplored in glaucoma models. This review focuses on some of the potential approaches for bioenergetic neuroprotection in the retina, including increasing the energy buffering capacity of damaged cells, decreasing the permeability of the mitochondrial membrane pore and free radical scavenging.
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PMID:Bioenergetic-based neuroprotection and glaucoma. 1870 Sep 28

Postherpetic neuralgia (PHN) is a chronic pain syndrome and one of the most common complications of herpes zoster. Although the pathophysiological mechanisms involved in PHN are still largely unknown, it seems reasonable to assume that there are lesions of the peripheral afferent pain pathways and inflammation-induced damage to afferent ganglia in the spinal cord. Growing body of evidence indicates that the glial cells, particularly microglia (CNS macrophages) and astrocytes are activated following peripheral and central noxious insult and their activation is thought to play an important role in central sensitization. Glial modulators showed antiallodynic and antihyperalgesic properties in various models of experimental pain. Minocycline is a semisynthetic second generation tetracycline that exerts neuroprotection effect. It has been shown to be effective in preventing sciatic inflammatory neuropathy and intrathecal HIV-1gp120 associated pain behaviors. This agent has been used recently as a selective microglial inhibitor since it prevents microglial activation and disease progression in experimental allergic encephalomyelitis, an animal model of multiple sclerosis and other neurodegenerative diseases, such as amyotropic lateral sclerosis and Parkinson's disease. Therefore, we hypothesize that minocycline might attenuate postherpetic neuralgia by specifically inhibiting the activation and metabolism of glial cells.
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PMID:Minocycline may attenuate postherpetic neuralgia. 1946 72

Restless legs syndrome (RLS) is a common movement disorder wherein sensory motor symptoms are observed in the limbs mainly during sleep and quiet wakefulness. The diagnostic criteria for RLS were established in 1995 by the International RLS Study Group (IRLSSG) and revised in 2003. The prevalence of RLS in Europe and North America was reported to be between 5% and 12%. On the other hand, the prevalence of RLS in Asia was lesser than that in Europe and North America: it was estimated to be less than 4%. This difference might be associated with vacial, cultural, and language differences. Genetic factors are known to contribute to the etiology of RLS in up to two-thirds of these patients. Furthermore, RLS might complicate an already existing medical condition. The development of secondary RLS is associated with renal failure, iron deficiency, frequent blood donation, Parkinson disease, neuropathy, as well as pregnancy. Generally, these medical condition are more frequently complicated in patient with RLS than in healthy controls. However, there is no conclusive evidence to prove an association between these medical conditions and RLS. Genetic contribution, environmental factors and other covariates such as gender, age, iron deficiency, as well as medical conditions play an important role in the development of RLS. In conclusion, epidemiological evidence suggests that both the primary and secondary forms of RLS are common neurological disorders. Future epidemiological studies are required to determine the potential risk factors contributing to the development of this disorder.
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PMID:[Prevalence of restless legs syndrome]. 1951 11

Restless legs syndrome (RLS) is a sensorimotor disorder, characterized by an irresistible urge to move the legs and usually accompanied or caused by uncomfortable and unpleasant sensations. It begins or worsens during periods of rest or inactivity, is partially or totally relieved by movement and is exacerbated or occurs mainly in the evening or night. People suffering from RLS are estimated to represent 2-3% of the general Japanese population, which is relatively lower than the estimated prevalence in western countries. Supportive diagnostic critevia include family history, the presence of periodic-leg movements (PLM) when awake or asleep, and a positive response to dopaminergic treatment. RLS phenotypes include an early onset form that is usually idiopathic with frequent familial history and a late onset form that is usually secondary to other somatic conditions that are causative factors in RLS occurrence. In all patients presenting with complaints of insomnia or discomfort in the lower limbs, diagnosis of RLS should be considered. RLS should be differentiated from akathisia, which is an urge to move the whole body in the absence of uncomfortable sensations. Polysomnographic studies and the suggested immobilization test (SIT) can detect PLM in patients that are asleep or awake. RLS may cause severe sleep disturbances, poor quality of life, depressive and anxious symptoms, and may be a risk factor for cardiovascular disease. Secondary RLS may occur due to iron deficiency, end-stage renal disease, pregnancy, peripheral neuropathy and drug use including antipsychotics and antidepressants. Small fiber neuropathy can trigger RLS or mimic its symptoms. RLS is associated with many neurological disorders, including Parkinson disease and multiple system atrophy; althoughit does not predispose to these diseases. A symptom rating scale for RLS authorized by the International RLS Study Group (IRLS) would facilitate accurate diagnosis of this condition.
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PMID:[Diagnosis and symptom rating scale of restless legs syndrome]. 1951 13

We report the case of a patient with Parkinson's disease who developed rapidly progressive weakness of the four limbs due to an acute motor axonal neuropathy (AMAN). This occurred days after a neuroleptic malignant syndrome (NMS). Serologic evidence of a preceding Campylobacter jejuni infection was detected and treatment with intravenous immunoglobulins proved effective. This case suggests that the rarely described neuropathies occurring with NMS may have a postinfectious immune basis and respond to immunomodulatory therapy.
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PMID:Neuroleptic malignant syndrome and acute motor axonal neuropathy after Campylobacter jejuni infection. 1971 63

While many treatments for mitochondrial electron transport (respiratory) chain disorders have been suggested, relatively few have undergone controlled clinical trials. This review focuses on the recent history of clinical trials of dichloroacetate (DCA), arginine, coenzyme Q(10), idebenone, and exercise in both primary (congenital) disorders and secondary (degenerative) disorders. Despite prior clinical impressions that DCA had a positive effect on mitochondrial disorders, two trials of diverse subjects failed to demonstrate a clinically significant benefit, and a trial of DCA in MELAS found a major negative effect of neuropathy. Arginine also has been used to treat MELAS with promising effects, although a controlled trial is still needed for this potentially toxic agent. The anti-oxidant coenzyme Q(10) is very widely used for primary mitochondrial disorders but has not yet undergone a controlled clinical trial; such a trial is now underway, as well as trials of the co-Q analogue idebenone for MELAS and LHON. Greater experience has accumulated with multi-center trials of coenzyme Q(10) treatment to prevent the progression of Parkinson disease. Although initial smaller trials indicated a benefit, this has not yet been confirmed in subsequent trials with higher doses; a larger Phase III trial is now underway. Similarly, a series of trials of idebenone for Friedreich ataxia have shown some benefit in slowing the progression of cardiomyopathy, and controlled clinical trials are now underway to determine if there is significant neurological protection. Uncontrolled trials of exercise showed an increase of exercise tolerance in patients with disorders of mitochondrial DNA, but did not selectively increase the percentage of normal mtDNA; a larger partially controlled trial is now underway to evaluate this possible benefit. In summary, none of the controlled trials so far has conclusively shown a benefit of treatment with the agents tested, but some promising therapies are currently being evaluated in a controlled manner. These experiences underscore the importance of controlled clinical trials for evaluation of benefits and risks of recommended therapies. Application of such clinical trials to future more effective therapies for mitochondrial disorders will require multi-center collaboration, organization, leadership, and financial and advocacy support.
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PMID:Treatment of mitochondrial electron transport chain disorders: a review of clinical trials over the past decade. 2006 Mar 49


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