title: Overexpression of p53 but not Rb in the cytoplasm of neurons and small vessels in an autopsy of a patient with Cockayne syndrome.
abstract: Cockayne syndrome presents senescence-like changes starting in early infancy; however, the mechanism of premature aging remains unclear. In an autopsy of a 23-year-old woman with Cockayne syndrome, we evaluated the correlation between Cockayne pathology and the expression patterns of the senescence-associated proteins p53 and Rb. Neuropathological findings in this case revealed basal ganglia calcification, tigroid leukodystrophy, bizarre reactive astrocytes, severe cerebellar atrophy with loss of Purkinje cells, and arteriolar/neuronal calcifications in the hypothalamus. Multiple arteriolar calcifications and sclerotic changes were seen in the central nervous system and kidney, but the endothelium of the aorta and coronary arteries remained intact appropriately for the individual's age without any finding of arteriosclerosis. Overexpression of p53 protein was confirmed in the cytoplasm of neurons in the basal ganglia, thalamus, hypothalamus, hippocampus and cerebellum, of arteriolar endothelial cells of the cerebrum and renal glomerular capillaries, and of cutaneous epithelial cells. The distribution of p53 overexpression was coincident with that of pathological alteration, such as neuronal loss, calcification and atrophy. High expression of p53 was localized in the cytoplasm, not in the nucleus. In contrast to p53, Rb was not expressed in any senescence lesion. In terms of senescence, distinct differences are found among organs in a patient with Cockayne syndrome. This segmental progeria differs from natural aging, and implicates p53 overexpression in the etiology of CS.
authors.affiliation: Department of Pediatrics, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyahara
authors.affiliation: Department of Pediatrics, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Itonaga
authors.affiliation: Department of Pediatrics, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Department of Pediatrics, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Izumi
authors.affiliation: Department of Pediatrics, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ihara
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003057:Cockayne Syndrome / Q000378:metabolism* / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D009474:Neurons / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53
keywords: Cockayne syndrome; Rb; aging; p53; progeria; senescence