title: Oxidative stress and disturbed glutamate transport in hereditary nucleotide repair disorders.
abstract: Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are hereditary DNA repair disorders complicated by progressive neurodegeneration. Here we immunohistochemically examine the in situ expression of materials that are produced by oxidative stress and glutamate transporters (which can contribute to prevention of glutamate neurotoxicity) in the brains of 5 autopsied patients each of XPA, CS, and control groups. All oxidative products, including nitrotyrosine, advanced glycation end product, and 4-hydroxy-2-nonenal-modified protein (HNE) were deposited in large amounts in the globus pallidus of CS patients compared to XPA patients. They were frequently recognized in the pseudocalcified foci and free minerals in the neuropil, and more rarely in foamy spheroids. In addition, the deposition of HNE was observed also in hippocampal and cerebellar dentate neurons of both CS and XPA patients. The expression of glial glutamate transporters, EAAT1 and GLT-1, was affected in the globus pallidus in 5 CS patients and 3 XPA patients. They were also altered in the cerebellar cortex in most of the CS patients. These data suggest that oxidative stress and disturbed glutamate transport may be involved in pallidal and/or cerebellar degeneration in hereditary nucleotide repair disorders.
authors: Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Japan.
authors: M
authors: M
authors: Hayashi
authors: M
authors: M
authors: Itoh
authors: S
authors: S
authors: Araki
authors: S
authors: S
authors: Kumada
authors: K
authors: K
authors: Shioda
authors: K
authors: K
authors: Tamagawa
authors: T
authors: T
authors: Mizutani
authors: Y
authors: Y
authors: Morimatsu
authors: M
authors: M
authors: Minagawa
authors: M
authors: M
authors: Oda
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D001692:Biological Transport; D002648:Child; D003057:Cockayne Syndrome / Q000378:metabolism* / Q000473:pathology; D004260:DNA Repair; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014983:Xeroderma Pigmentosum / Q000378:metabolism* / Q000473:pathology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000447:Aldehydes; D027322:Amino Acid Transport System X-AG; D017127:Glycation End Products, Advanced; D011506:Proteins; C002744:3-nitrotyrosine; D018698:Glutamic Acid; D014443:Tyrosine; C027576:4-hydroxy-2-nonenal