Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of the aminotransferases, GOT and GPT, were determined in the serum and cerebrospinal fluid of patients with Parkinson's disease, Huntington's chorea, Wilson's disease, amyotrophic lateral sclerosis (ALS), Friedreich's ataxia, phenylketonuria, and head injuries. 1. In patients with Huntington's chorea the activity of SGOT was lower than in controls (P = 0.02); in Friedreich's ataxia LGPT activity was decreased (P less than 0.001); in patients suffering from ALS SGOT (P = 0.005), SGPT (P less than 0.001) and LGOT (P less than 0.001) activities were increased. 2. Long-term treatment of Parkinson's disease and Wilson's disease with L-dopa resulted in an increase in SGOT, LGOT, and SGPT activity over approximately 2 months, with subsequent normalization of these enzyme activities in spite of continued therapy. Guanidine treatment led to an increase in aminotransferase activities in patients with ALS. Penicillamine caused a decrease in SGOT and SGPT activities in Wilson's disease. These results illustrate the necessity of taking therapeutic measures into account in the interpretation of data on aminotransferase activities.
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PMID:[The activity of aminotransferases in serum and cerebrospinal fluid in neurological diseases (author's transl)]. 12 63

Motor evoked potentials (MEPs) to transcranial stimulation (TCS) and somatosensory evoked potentials to median nerve stimulation (MN-SEPs) were examined in 74 patients affected by multiple sclerosis (MS = 49 cases), amyotrophic lateral sclerosis (ALS = 9 cases), cervical cord lesions (7 cases), Parkinson's disease (PD = 5 cases), Huntington's chorea (HC = 2 cases), Wilson's disease (WD = 1 case), subacute combined degeneration (SCD = 1 case). MN-SEPs were altered in 38% of arms in MS with a higher incidence in clinically affected than in clinically 'silent' arms (= 77.8% vs. 27.5%). MEP alterations were found in 54% of examined arms, mostly because of a prolongation of the motor CCT. This index was invariably altered in the affected arms, whilst it was involved in 40% of the 'silent' ones. Twelve out of 18 arms displayed abnormal MEPs in ALS. These were mainly due to an absent response, even if moderate motor CCT prolongation and 'giant' MEPs were also encountered. MN-SEPs were altered in 3/18 arms. By recording MEPs from proximal and distal upper limb muscles, cues on the level of abnormal propagation were obtained in patients suffering from 'focal' lesions of the spinal cord. Combining SEP records enhanced the diagnostic yield in this field. Both MEPs and SEPs were normal in patients with PD and HC, whilst abnormally prolonged CCTs were found in the case with WD. MEP and SEP recording revealed central propagation abnormalities coupled to a severe clinical picture of the peripheral nerve involvement (as in the case of SCD).
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PMID:Neurophysiological evaluation of the central nervous impulse propagation in patients with sensorimotor disturbances. 245 26

The serum level of ceruloplasmin and copper were determined in 14 patients with ALS, 9 with Wilson's disease and 10 with other brain diseases. The enzyme level in 8 patients with ALS (57%) was decreased, similarly as in 8 with Wilson's disease (89%), and 2 (20%) in the control group. The mean ceruloplasmin level in the group of patients with Wilson's disease was 50% that in ALS patients. The copper level was decreased in only 1 ALS patient and 1 in the control group, while in patients with Wilson's disease it was low in 8 cases. These changes may be an effect as well as a cause of motor neuron disease.
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PMID:[Ceruloplasmin and copper in the serum of patients with amyotrophic lateral sclerosis (ALS)]. 664 24

We used a paired-pulse magnetic stimulation technique to study ipsilateral cortico-cortical inhibition of the motor cortex in 48 patients with various neurological disorders and in 20 normal volunteers. In the normal subjects, the first subthreshold conditioning stimulus suppressed responses to the second suprathreshold test stimulus at interstimulus intervals (ISIs) of 1-5 ms (inhibition at short intervals), and facilitated them at ISIs of 8-15 ms (facilitation at long intervals). Patients with motor neuron disease, except those in whom brain stimulation produced control responses that were generated by direct activation of corticospinal neurons (D-waves), had normal inhibition at short intervals. Facilitation at long intervals was not elicited in some patients with amyotrophic lateral sclerosis. Less inhibition at short intervals and normal facilitation at long intervals was found for all the patients with progressive myoclonic epilepsy, a condition in which the excitability of cortical inhibitory interneurons is thought to be affected. Inhibition at short intervals was disturbed, but facilitation at long intervals was intact in the patients with movement disorders (Parkinson's disease, corticobasal degeneration, and Wilson's disease). In these patients, positron emission tomography (PET) studies showed decreased regional cerebral blood flow (rCBF) in the basal ganglia in the relaxed state. However, normal suppression was elicited in the patients with Parkinson's disease with normal rCBF. In four patients with chorea, the time-course of inhibition and facilitation was normal, even though PET studies showed decreased rCBF in the basal ganglia in two of them. Normal inhibition could not be elicited in patients who had a small lesion in the basal ganglia or in the pathway from basal ganglia to the primary motor cortex; the putamen, globus pallidus, and supplementary motor cortex. In contrast, patients who had a lesion in a sensory system (sensory cortex or sensory thalamus) or in the pontine nucleus had normal suppression. We conclude that the results of ipsilateral cortico-cortical inhibition with paired magnetic stimulation reflect the excitability of inhibitory interneurons in the motor cortex and that outputs from the basal ganglia markedly affect this inhibition, but outputs from somato-sensory systems or cerebellum do not. Moreover, dysfunction of the corticospinal tract or spinal motoneurons does not affect results obtained by the paired magnetic stimulation technique when the control responses are generated by I-waves (i.e. descending volleys are produced by transsynaptic activation of the corticospinal tract neurons.
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PMID:Ipsilateral cortico-cortical inhibition of the motor cortex in various neurological disorders. 886 35

Mitochondria have been linked to both necrotic and apoptotic cell death, which are thought to have a major role in the pathogenesis of neurodegenerative diseases. Recent evidence shows that nuclear gene defects affecting mitochondrial function have a role in the pathogenesis of Friedreich's ataxia, Wilson's disease and hereditary spastic paraplegia. There is also accumulating evidence that mitochondrial dysfunction might have a role in the pathogenesis of amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and Alzheimer's disease. If this is so, a number of therapeutic targets are implicated that might result in novel treatments for neurodegenerative diseases.
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PMID:Energetics in the pathogenesis of neurodegenerative diseases. 1085 39

Copper is an essential trace element, but its redox reactivity leads to risks of damage to cell and tissues. These are well exemplified by several forms of neurodegenerative diseases, either arising as inherited disorders of copper metabolism, such as Menkes' and Wilson's disease, or as conformational diseases such as Alzheimer's disease and prion diseases. This review will cover some aspects of the involvement of copper-mediated oxidative stress in degenerative processes in the central nervous system, with special focus on the familial form of amyotrophic lateral sclerosis (FALS). Furthermore, a possible role of copper reactivity in inducing critical steps in the apoptotic pathways leading to neurodegeneration is envisaged.
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PMID:Copper-dependent oxidative stress and neurodegeneration. 1132 25

Metallothioneins (MTs) are ubiquitous metal-binding proteins that have been highly conserved throughout evolution. Although their physiological function is not completely understood, they are involved in diverse processes including metal homeostasis and detoxification, the oxidative stress response, inflammation, and cell proliferation. Te human MT gene family consists of at least 18 isoforms, containing pseudogenes as well as genes encoding functional proteins. Most of the MT isoforms can be induced by a wide variety of substances, such as metals, cytokines, and hormones. Different cell types express discrete MT isoforms, which reflects the specifically adapted functions of MTs and a divergence in their regulation. Te aberrant expression of MTs has been described in a number of diseases, including Crohn's disease, cancer, Alzheimer's disease, amyotrophic lateral sclerosis, Menkes disease, and Wilson's disease. Therefore, a thorough understanding of MT gene regulation is imperative. To date, the transcriptional regulation of MTs has primarily been studied in mice. While only four murine MT isoforms exist, the homology between murine and human MTs allows for the evaluation of the regulatory regions in their respective promoters. Here, we review the aberrant expression of MTs in human diseases and the mechanisms that regulate MT1 expression based on an in silico evaluation of transcription factor binding sites.
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PMID:Human metallothionein expression under normal and pathological conditions: mechanisms of gene regulation based on in silico promoter analysis. 1981 7

Homeostasis of metal ions such as Zn(2+) is essential for proper brain function. Moreover, the list of psychiatric and neurodegenerative disorders involving a dysregulation of brain Zn(2+)-levels is long and steadily growing, including Parkinson's and Alzheimer's disease as well as schizophrenia, attention deficit and hyperactivity disorder, depression, amyotrophic lateral sclerosis, Down's syndrome, multiple sclerosis, Wilson's disease and Pick's disease. Furthermore, alterations in Zn(2+)-levels are seen in transient forebrain ischemia, seizures, traumatic brain injury and alcoholism. Thus, the possibility of altering Zn(2+)-levels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. Although the role of Zn(2+) in the brain has been extensively studied over the past decades, methods for controlled regulation and manipulation of Zn(2+) concentrations within the brain are still in their infancy. Since the use of dietary Zn(2+) supplementation and restriction has major limitations, new methods and alternative approaches are currently under investigation, such as the use of intracranial infusion of Zn(2+) chelators or nanoparticle technologies to elevate or decrease intracellular Zn(2+) levels. Therefore, this review briefly summarizes the role of Zn(2+) in psychiatric and neurodegenerative diseases and highlights key findings and impediments of brain Zn(2+)-level manipulation. Furthermore, some methods and compounds, such as metal ion chelation, redistribution and supplementation that are used to control brain Zn(2+)-levels in order to treat brain disorders are evaluated.
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PMID:Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review. 2210 82

The past decade has witnessed an explosion of evidence suggesting that many neurodegenerative diseases can be detected years, if not decades, earlier than previously thought. To date, these scientific advances have not provoked any parallel translational or clinical improvements. There is an urgency to capitalize on this momentum so earlier detection of disease can be more readily translated into improved health-related quality of life for families at risk for, or suffering with, neurodegenerative diseases. In this review, we discuss health-related quality of life (HRQOL) measurement in neurodegenerative diseases and the importance of these "patient reported outcomes" for all clinical research. Next, we address HRQOL following early identification or predictive genetic testing in some neurodegenerative diseases: Huntington disease, Alzheimer's disease, Parkinson's disease, Dementia with Lewy bodies, frontotemporal dementia, amyotrophic lateral sclerosis, prion diseases, hereditary ataxias, Dentatorubral-pallidoluysian atrophy and Wilson's disease. After a brief report of available direct-to-consumer genetic tests, we address the juxtaposition of earlier disease identification with assumed reluctance toward predictive genetic testing. Forty-one studies examining health-related outcomes following predictive genetic testing for neurodegenerative disease suggested that (a) extreme or catastrophic outcomes are rare; (b) consequences commonly include transiently increased anxiety and/or depression; (c) most participants report no regret; (d) many persons report extensive benefits to receiving genetic information; and (e) stigmatization and discrimination for genetic diseases are poorly understood and policy and laws are needed. Caution is appropriate for earlier identification of neurodegenerative diseases but findings suggest further progress is safe, feasible and likely to advance clinical care.
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PMID:A review of quality of life after predictive testing for and earlier identification of neurodegenerative diseases. 2403 31

Copper is a biometal essential for normal brain development and function, thus copper deficiency or excess results in central nervous system disease. Well-characterized disorders of disrupted copper homoeostasis with neuronal degeneration include Menkes disease and Wilson's disease but a large body of evidence also implicates disrupted copper pathways in other neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, Amyotrophic lateral sclerosis, Huntington's disease and prion diseases. In this short review we critically evaluate the data regarding changes in systemic and brain copper levels in Parkinson's disease, where alterations in brain copper are associated with regional neuronal cell death and disease pathology. We review copper regulating mechanisms in the human brain and the effects of dysfunction within these systems. We then examine the evidence for a role for copper in pathogenic processes in Parkinson's disease and consider reports of diverse copper-modulating strategies in in vitro and in vivo models of this disorder. Copper-modulating therapies are currently advancing through clinical trials for Alzheimer's and Huntington's disease and may also hold promise as disease modifying agents in Parkinson's disease.
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PMID:Copper dyshomoeostasis in Parkinson's disease: implications for pathogenesis and indications for novel therapeutics. 2695 44


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