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)

Neurophysiological studies were performed on 8 patients with group A xeroderma pigmentosum during early childhood. EEG, ABR and NCV were normal during this period. In contrast, various sleep parameters detected by polysomnography showed abnormal findings even in the neurologically normal patient. Decreased % sleep REM was seen in a case, and decreased frequency of REMs were seen in another. Body movements were extremely high or low in frequency in 3 cases in whole night sleep. The distribution of body movements were abnormal; in control subjects, the frequency was higher in SREM and stage 1 than in slow wave sleep; in 7 cases, it was higher in slow wave sleep than in stage 1 or 2, or body movements were extremely frequent. Neurological examination revealed soft signs in various systems in early childhood. All cases except one showed hypotonia. Many cases were slow in learning to walk and the gait was unstable. Speech delay and decreased deep tendon reflexes, especially of patella, were seen in most cases. Since the neural deficits in XP may be related to the DNA repair defect, these findings indicate the possibility that some endogenous compounds distributing all over the nervous system might produce the DNA damages. Because the body movements during sleep are controlled by the nigrostriatal dopaminergic system, present data indicate that the basal ganglia might be one of the earliest degenerative systems in the CNS. Recently, some studies have suggested the possibility that oxygen radical mechanisms might be involved in the development of the dopamine neurodegenerative process in Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Neurophysiological studies on group A xeroderma pigmentosum in early childhood]. 217 31

Since 1999, oxidative damage to RNA molecules has been described in several neurological diseases including Alzheimer's disease, Parkinson's disease, Down syndrome, dementia with Lewy bodies, prion disease, subacute sclerosing panencephalitis, and xeroderma pigmentosum. An early involvement of RNA oxidation of vulnerable neuronal population in the neurodegenerative diseases has been demonstrated, which is strongly supported by a recent observation of increased RNA oxidation in brains of subjects with mild cognitive impairment. Until recently, little is known about consequences and cellular handling of the RNA damage. However, increasing body of evidence suggests detrimental effects of the RNA damage in protein synthesis and the existence of several coping mechanisms including direct repair and avoiding the incorporation of the damaged ribonucleotides into translational machinery. Further investigations toward understanding of the consequences and cellular handling mechanisms of the oxidative RNA damage may provide significant insights into the pathogenesis and therapeutic strategies of the neurodegenerative diseases.
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PMID:Oxidative damage to RNA in neurodegenerative diseases. 1704 15

In this Review, familial and sporadic neurological disorders reported to have an etiological link with DNA repair defects are discussed, with special emphasis placed on the molecular link between the disease phenotype and the precise DNA repair defect. Of the 15 neurological disorders listed, some of which have symptoms of progeria, six--spinocerebellar ataxia with axonal neuropathy-1, Huntington's disease, Alzheimer's disease, Parkinson's disease, Down syndrome and amyotrophic lateral sclerosis--seem to result from increased oxidative stress, and the inability of the base excision repair pathway to handle the damage to DNA that this induces. Five of the conditions (xeroderma pigmentosum, Cockayne's syndrome, trichothiodystrophy, Down syndrome, and triple-A syndrome) display a defect in the nucleotide excision repair pathway, four (Huntington's disease, various spinocerebellar ataxias, Friedreich's ataxia and myotonic dystrophy types 1 and 2) exhibit an unusual expansion of repeat sequences in DNA, and four (ataxia-telangiectasia, ataxia-telangiectasia-like disorder, Nijmegen breakage syndrome and Alzheimer's disease) exhibit defects in genes involved in repairing double-strand breaks. The current overall picture indicates that oxidative stress is a major causative factor in genomic instability in the brain, and that the nature of the resulting neurological phenotype depends on the pathway through which the instability is normally repaired.
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PMID:Mechanisms of disease: DNA repair defects and neurological disease. 1734 92

The accumulation of DNA damage has been widely implicated in premature aging and neurodegeneration. Progeroid syndromes with defects in the cellular response to DNA damage suggest that progressive genome instability represents an important aspect of the aging process. Moreover, most of the major neurodegenerative diseases are characterized by the accumulation of neuronal DNA damage, suggesting that impaired DNA repair mechanisms might be relevant to both premature aging and neurodegeneration. Two progeroid syndromes, Hutchinson-Gilford progeria syndrome and Werner's syndrome, are characterized by clinical features mimicking physiological aging at an early age and molecular studies have implicated decreased cell proliferation and altered DNA-damage responses as common causal mechanisms in the pathogenesis of both diseases. Defects in nucleotide excision repair cause three distinct human diseases: xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy; each of them is characterized by premature onset of pathologies that overlap with those associated with old age in humans. Increasing evidence also suggests that an impaired DNA repair, particularly the base excision repair pathway, might play a fundamental role in the development of age-related neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington' s disease. Here, we review the current knowledge on the role of DNA repair in premature aging and neurodegenerative diseases.
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PMID:DNA repair in premature aging disorders and neurodegeneration. 2029 65

Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby causing Huntington's disease. Single-strand breaks are common DNA lesions and are associated with the neurodegenerative diseases, ataxia-oculomotor apraxia-1 and spinocerebellar ataxia with axonal neuropathy-1. DNA double-strand breaks are toxic lesions and two main pathways exist for their repair: homologous recombination and non-homologous end-joining. Ataxia telangiectasia and related disorders with defects in these pathways illustrate that such defects can lead to early childhood neurodegeneration. Aging is a risk factor for neurodegeneration and accumulation of oxidative mitochondrial DNA damage may be linked with the age-associated neurodegenerative disorders Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Mutation in the WRN protein leads to the premature aging disease Werner syndrome, a disorder that features neurodegeneration. In this article we review the evidence linking deficiencies in the DNA repair pathways with neurodegeneration.
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PMID:DNA repair deficiency in neurodegeneration. 2155 Mar 79

A large number of studies indicate that DNA damage and mutation increase with age in human cells and tissues (1). Age-related degenerative disorders in which DNA damage has been invoked include heart disease and neurodegenerative conditions such as Alzheimer's disease, amyotrophic lateral sclerosis, or Parkinson's disease (2, 3). Patients with deficiencies in DNA repair, including xeroderma pigmentosum (XP) (4) and ataxia-telangiectasia (A-T) (5) show characteristic patterns of neurodegeneration (as opposed to a failure of normal development). The implication is that failure of repair can lead to accumulation of damage and degenerative disease. XPs and A-Ts are hypersensitive to specific types of DNA damage, and the degenerative damage in patients is tissue specific. DNA in every tissue, however, is under attack from a range of endogenously formed mutagens, including reactive oxygen species, nitric oxide, reactive metabolites, and breakdown products such as malondialdehyde. A series of repair enzymes recognize and remove these types of DNA damage from the genome. Failure to repair DNA may cause the synthesis of defective proteins, which will repair DNA less efficiently, and in turn lead to propagation of further errors (6). Alternatively, oxidative damage to mitochondrial proteins might cause less efficient processing of oxygen, release of higher levels of reactive oxygen species and increased levels of background DNA damage.
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PMID:Measurement of DNA damage and repair capacity as a function of age using the comet assay. 2235 Dec 71

AlkB family proteins are enzymes that repair alkylated DNA and RNA by oxidative demethylation. Nine homologs have been identified and characterized in mammals. ALKBH1 is conserved among metazoans including Drosophila. Although the ALKBH1 mouse homolog, Alkbh1 functions in neurogenesis, it currently remains unclear whether ALKBH1 plays a role in neuronal disorders induced by ultraviolet-induced DNA damage. We herein demonstrated that the Drosophila ALKBH1 homolog, AlkB contributed to recovery from neuronal disorders induced by ultraviolet damage. The knockdown of AlkB resulted in not only learning defects but also altered crawling behavior in Drosophila larvae after ultraviolet irradiation. A molecular analysis revealed that AlkB contributed to the repair of ultraviolet-induced DNA damage in the central nervous system of larvae. Therefore, we propose that ALKBH1 plays a role in the repair of ultraviolet-induced DNA damage in central nervous system. Ultraviolet-induced DNA damage is involved in the pathogenesis of xeroderma pigmentosum, and has recently been implicated in Parkinson's disease. The present results will contribute to our understanding of neuronal diseases induced by ultraviolet-induced DNA damage.
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PMID:Drosophila Alpha-ketoglutarate-dependent dioxygenase AlkB is involved in repair from neuronal disorders induced by ultraviolet damage. 3150 4