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)

Reactive oxygen species, such as superoxide radicals, are thought to underlie the pathogenesis of various diseases. Almost 3 to 10% of the oxygen utilized by tissues is converted to its reactive intermediates, which impair the functioning of cells and tissues. Superoxide dismutase (SOD) catalyzes the conversion of single electron reduced species of molecular oxygen to hydrogen peroxide and oxygen. There are several classes of SOD that differ in their metal binding ability, distribution in different cell compartments, and sensitivity to various reagents. Among these, Cu, Zn superoxide dismutase (SOD1) is widely distributed and comprises 90% of the total SOD. This ubiquitous enzyme, which requires Cu and Zn for its activity, has great physiological significance and therapeutic potential. The present review describes the role of SODs, especially Cu, Zn SOD, in several diseases, such as familial amyotrophic lateral sclerosis (FALS), Parkinson's disease, Alzheimer's disease, dengue fever, cancer, Down's syndrome, cataract, and several neurological disorders. Mutations in the SOD1 gene cause a familial form of amyotrophic lateral sclerosis. The mechanism by which mutant SOD1 causes the degeneration of motor neurons is not well understood. Transgenic mice expressing multiple copies of FALS-mutant SOD1s develop an ALS-like motor neuron disease. Vacuolar degeneration of mitochondria has been identified as the main pathological feature associated with motor neuron death and paralysis in several lines of FALS-SOD1 mice. Various observations and conclusions linking mutant SOD1 and FALS are discussed in this review in detail.
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PMID:Superoxide dismutase--applications and relevance to human diseases. 1221 58

Neurodegenerative diseases (NDD) are a group of illness with diverse clinical importance and etiologies. NDD include motor neuron disease such as amyotrophic lateral sclerosis (ALS), cerebellar disorders, Parkinson's disease (PD), Huntington's disease (HD), cortical destructive Alzheimer's disease (AD) and Schizophrenia. Numerous epidemiological and experimental studies provide many risk factors such as advanced age, genetic defects, abnormalities of antioxidant enzymes, excitotoxicity, cytoskeletal abnormalities, autoimmunity, mineral deficiencies, oxidative stress, metabolic toxicity, hypertension and other vascular disorders. Growing body of evidence implicates free radical toxicity, radical induced mutations and oxidative enzyme impairment and mitochondrial dysfunction due to congenital genetic defects in clinical manifestations of NDD. Accumulation of oxidative damage in neurons either primarily or secondarily may account for the increased incidence of NDD such as AD, ALS and stroke in aged populations. The molecular mechanisms of neuronal degeneration remain largely unknown and effective therapies are not currently available. Recent interest has focused on antioxidants such as carotenoids and in particular lycopene, a potent antioxidant in tomatoes and tomato products, flavonoids and vitamins as potentially useful agents in the management of human NDD. The pathobiology of neurodegenerative disorders with emphasis on genetic origin and its correlation with oxidative stress of neurodegenerative disorders will be reviewed and the reasons as to why brain constitutes a vulnerable site of oxidative damage will be discussed. The article will also discuss the potential free radical scavenger, mechanism of antioxidant action of lycopene and the need for the use of antioxidants in the prevention of NDD.
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PMID:Role of oxidative stress and antioxidants in neurodegenerative diseases. 1238 92

Alzheimer's disease, Parkinson's disease, and motor neuron disease share a propensity to occur with increasing age and as either a sporadic or a familial disorder. A number of behavioral and environmental risk factors have been proposed for each disorder, but most associations lack consistency and specificity. Over the last decade the remarkable frequency of these disorders has become apparent, and the identification of mutations in genes has provided the means to understand their pathogenesis. Better and more accurate means to characterize and diagnose these diseases has greatly facilitated analytic epidemiology. The analysis of behavioral and genetic factors that may lower disease risk has led to clinical trials that are either in progress or being planned with the aim of preventing these disorders.
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PMID:Epidemiology of neurodegeneration. 1257 95

The past few years have been marked by substantial progress in preclinical studies of therapeutic gene transfer for neurologic disease using viral-based vectors. In this article, the authors review the data regarding (1). treatment of focal neuronal degeneration, exemplified by Parkinson disease, ischemia, and trauma models; (2). treatment of global neurologic dysfunction, exemplified by the mucopolysaccharidoses and other storage diseases; (3). peripheral nervous system diseases including motor neuron disease and sensory neuropathies; and (4). the use of vectors expressing neurotransmitters to modulate functional neural activity in the treatment of pain. The results suggest that a number of different viral vectors may be appropriate for gene transfer to the central nervous system for specific disease processes, and that for the peripheral nervous system herpes simplex virus-based vectors appear to have special utility. The results of the first human gene therapy trials for neurologic disease, which are just now beginning, will be crucial in defining the next step in the development of this therapy.
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PMID:Therapeutic gene transfer to the nervous system using viral vectors. 1270 47

Vacuole-creating protein (VCP) is a member of the ATPases associated with diverse cellular activities and is a putative sensor protein for degenerative proteins. Immunohistochemical examinations demonstrated that VCP was observed in ubiquitin-positive intraneuronal inclusions in motor neuron disease with dementia, ballooned neurons in Creutzfeldt-Jakob disease, dystrophic neurites of senile plaque in Alzheimer's disease, and Lewy and Marinesco bodies and Lewy neurites in Parkinson's disease, while granules of granulovacuolar degeneration and neurofibrillary tangles in Alzheimer's disease were not positively stained for VCP. These results indicate that VCP reacts with abnormal or misfolded proteins and plays a role in accelerating the process of degeneration and cell death. The elucidation of an association between VCP and these degenerative proteins will provide an important clue for understanding common mechanisms underlying neurodegenerative diseases.
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PMID:Vacuole-creating protein in neurodegenerative diseases in humans. 1275 68

The major causes of the common neurodegenerative diseases remain unknown. Alzheimer's disease, Parkinson's disease and motor neuron disease occur in both sporadic and familial forms, and mutations are progressively being found in families with these disorders. However, attempts to find causative mutations in blood DNA from the sporadic forms of the diseases have proved fruitless. It is hypothesised that this is because the causative mutations are found only in the cells in the central nervous system that are affected by the disease. These mutations arise in the developing embryo in progenitor cells of neurons or glia. The diseases are not passed to offspring since the mutations are not present in the germ-line. To find somatic mutations, the affected central nervous system cells need to be separated out and submitted to DNA analysis.
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PMID:Somatic mutation: a cause of sporadic neurodegenerative diseases? 1508 89

Alzheimer's disease (AD) is the commonest neurodegenerative disease worldwide. Rare familial cases may be caused by mutations in one of three genes-amyloid precursor protein, presenilin-1 and presenilin-2; however, the molecular basis of >99% of AD cases is unknown. Somatic mutation has been considered to be a mechanism that may account for a proportion of sporadic cases of AD, but to date there has been no evidence for this. We now report a sporadic early-onset patient with AD, and show that this individual is a somatic mosaic for a mutation in the presenilin-1 gene, suggesting a novel molecular mechanism for AD. Quantification of the mosaicism demonstrated the degree of mosaicism at 8% in peripheral lymphocytes and 14% in cerebral cortex in the index patient; a clear gene dosage effect on age of presentation and clinical phenotypic presentation is demonstrated. This finding has important implications for the aetiology of sporadic AD, and for other apparently sporadic neurodegenerative diseases such as Parkinson's disease, motor neuron disease and Creutzfeldt-Jakob disease.
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PMID:Somatic and germline mosaicism in sporadic early-onset Alzheimer's disease. 1511 57

Neurodegeneration induced by excitatory neurotransmitter glutamate is considered to be of particular relevance in several types of acute and chronic neurological impairments ranging from cerebral ischaemia to neuropathological conditions such as motor neuron disease, Alzheimer's, Parkinson's disease and epilepsy. The hyperexcitation of glutamate receptors coupled with calcium overload can be prevented or modulated by using well-established competitive and non-competitive antagonists targeting ion/receptor channels. The exponentially increasing body of pharmacological evidence over the years indicates potential applications of peptide toxins, due to their exquisite subtype selectivity on ion channels and receptors, as lead structures for the development of drugs for the treatment of wide variety of neurological disorders. This review comprehensively highlights the overview of the diversity in the molecular as well as neurobiological mechanisms of different peptide toxins derived from venomous animals with particular reference to neuroprotection. In addition, the potential applications of peptide toxins in the diagnosis and treatment of neurological disorders such as neuromuscular disorders, epilepsy, Alzheimer's and Parkinson's diseases, gliomas and ischaemic stroke and their future prospects in the diagnosis as well as in the therapy are addressed.
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PMID:Neuroprotection and peptide toxins. 1514 23

Spinocerebellar ataxia type 2 (SCA2) has been recognized recently as an uncommon cause of parkinsonism, an alternate presentation to the typical cerebellar disorder. This research review summarizes the existing literature on parkinsonism-predominant presentation SCA2 and presents new clinical cases of patients with this condition. Various phenotypes are noted in this subtype of SCA2, including parkinsonism indistinguishable from idiopathic Parkinson's disease (PD), parkinsonism plus ataxia, motor neuron disease, and postural tremor. In several kindreds with multiple affected family members, the SCA2 expansion segregated with disease; in addition, several single cases of parkinsonism with and without a family history are also described. The number of repeats in symptomatic patients ranged from 33 to 43. Interruption of the CAG repeat with CAA, CGG, or CCG was found in some individuals, possibly stabilizing the repeat structure and accounting for the relative stability of the repeat size across generations in some families; allele length is not necessarily indicative of trinucleotide repeat architecture. Positron emission tomography scanning in one family showed reduced fluorodopa uptake and normal to increased raclopride binding with a rostrocaudal gradient similar to that found in idiopathic PD. This review emphasizes the importance of testing for SCA2 in patients with parkinsonism and a family history of neurodegenerative disorders. Testing for SCA2 is also important in studies of inherited parkinsonism.
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PMID:Profile of families with parkinsonism-predominant spinocerebellar ataxia type 2 (SCA2). 1519 99

The prevalence of gait disorders among neurological inpatients is unknown, although disturbed gait is a common symptom. Gait disorders often lead to loss of independence with restraints for the patients and caregivers and costs for the health system. We designed a prospective study and investigated all patients admitted to a neurological hospital during a 100-day period for the presence of a gait disorder. Clinical investigation and several disease-specific rating scales were carried out for 493 patients. In 60% of the patients, a disturbance of gait was diagnosed. Most frequent diagnoses were stroke (21%), Parkinson's disease (17%), and polyneuropathy (7%). Within these diagnoses, the rate of patients with disturbed gait was high in Parkinson's disease (93%), subcortical arteriosclerotic encephalopathy (85%), and motor neuron disease (83%). Advanced age, dementia, alcohol abuse, and treatment with antiepileptics, neuroleptics, benzodiazepines, and chemotherapeutics were identified as risk factors for a gait disorder. A decline of cognitive function was accompanied by a reduction of walking speed. According to these results, gait disorders are among the most frequent symptoms in neurology.
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PMID:Prevalence of gait disorders in hospitalized neurological patients. 1539 43


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