Cerebellar neurodegeneration in human hereditary DNA repair disorders

Kohji, Toshihiko; Hayashi, Masaharu; Shioda, Kei; Minagawa, M; Morimatsu, Yoshio; Tamagawa, Kimiko; Oda, Masaya

doi:10.1016/s0304-3940(98)00109-8

Cited by 40 publications

(30 citation statements)

References 14 publications

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“…The reported neurotrophic activities on CG cells in vitro also point out important implications for cerebellar neurodegenerative diseases, e.g. xeroderma pigmentosum and Cockayne syndrome, hereditary disorders characterized by impaired DNA repair and neurodegeneration, in particular apoptosis of CG neurons (45). Although the protein is detected in cerebrospinal fluid (8), we have not detected it in the CG cell culture media, 3 suggesting that PEDF could be a paracrine neurotrophic factor for cerebellar neurons.…”

Section: Discussionmentioning

confidence: 77%

Binding of Pigment Epithelium-derived Factor (PEDF) to Retinoblastoma Cells and Cerebellar Granule Neurons

Alberdi¹,

Aymerich

Becerra

1999

Journal of Biological Chemistry

118

127

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Section: Discussionmentioning

confidence: 77%

Binding of Pigment Epithelium-derived Factor (PEDF) to Retinoblastoma Cells and Cerebellar Granule Neurons

Alberdi¹,

Aymerich

Becerra

1999

Journal of Biological Chemistry

118

127

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“…Faulty repair of oxidative damage from normal metabolism can result in an accumulation of defective residues that can contribute to premature cell death by apoptosis. 60,64,[67][68][69] Cockayne syndrome cells respond poorly to oxidative stress. 70 Whether mitochondrial dysfunction plays a role in hearing loss, retinitis pigmentosa, and other manifestations of Cockayne syndrome remains to be determined.…”

Section: Pathophysiologymentioning

confidence: 99%

Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

et al. 2006

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Cockayne syndrome and xeroderma pigmentosum-Cockayne syndrome complex are rare autosomal recessive disorders with poorly understood biology. They are characterized by profound postnatal brain and somatic growth failure and by degeneration of multiple tissues resulting in cachexia, dementia, and premature aging. They result in premature death, usually in childhood, exceptionally in adults. This study compares the clinical course and pathology of a man with Cockayne syndrome group A who died at age 31½ years with 15 adequately documented other adults with Cockayne syndrome and 5 with xeroderma pigmentosum-Cockayne syndrome complex. Slowing of head and somatic growth was apparent before age 2 years, mental retardation and slowly progressive spasticity at 4 years, ataxia and hearing loss at 9 years, visual impairment at 14 years, typical Cockayne facies at 17 years, and cachexia and dementia in his twenties, with a retained outgoing personality. He experienced several transient right and left hemipareses and two episodes of status epilepticus following falls. Neuropathology disclosed profound microencephaly, bilateral old subdural hematomas, white-matter atrophy, tigroid leukodystrophy with string vessels, oligodendrocyte proliferation, bizarre reactive astrocytes, multifocal dystrophic calcification that was most marked in the basal ganglia, advanced atherosclerosis, mixed demyelinating and axonal neuropathy, and neurogenic muscular atrophy. Cellular degeneration of the organ of Corti, spiral and vestibular ganglia, and all chambers of the eye was severe. Rarely, and for unexplained reasons, in some patients with Cockayne syndrome the course is slower than usual, resulting in survival into adulthood. The profound dwarfing, failure of brain growth, cachexia, selectivity of tissue degeneration, and poor correlation between genotypes and phenotypes are not understood. Deficient repair of DNA can increase vulnerability to oxidative stress and play a role in the premature aging, but why patients with mutations in xeroderma pigmentosum genes present with the Cockayne syndrome phenotype is still not known.

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“…This is caused by neurodegeneration in the cerebral cortex, basal ganglia, cerebellum, brain stem, corticospinal tract, cochlea, dorsal root ganglia and peripheral nerves (Hayashi et al, 2004;Robbins et al, 1991;Robbins et al, 2002). Loss of neurons is due to apoptotic cell death (Kohji et al, 1998), presumably as a consequence of failure to repair endogenous DNA damage. Myelination, or white matter is not affected (Hentati et al, 1992) nor are glial cells (Kohji et al, 1998).…”

Section: Nervous Systemmentioning

confidence: 99%

“…Loss of neurons is due to apoptotic cell death (Kohji et al, 1998), presumably as a consequence of failure to repair endogenous DNA damage. Myelination, or white matter is not affected (Hentati et al, 1992) nor are glial cells (Kohji et al, 1998). Accordingly, in vitro primary neurons from Xpa −/− mice are significantly more sensitive to genotoxic stress than astroglial cells (Kisby et al, 2004).…”

Section: Nervous Systemmentioning

confidence: 99%

Tissue-specific accelerated aging in nucleotide excision repair deficiency

Niedernhofer

2008

Mechanisms of Ageing and Development

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Nucleotide excision repair (NER) is a multi-step DNA repair mechanism that removes helixdistorting modified nucleotides from the genome. NER is divided into two subpathways depending on the location of DNA damage in the genome and how it is first detected. Global genome NER identifies and repairs DNA lesions throughout the genome. This subpathway of NER primarily protects against the accumulation of mutations in the genome. Transcription-coupled (TC) NER rapidly repairs lesions in the transcribed strand of DNA that block transcription by RNA polymerase II. TC-NER prevents cell death in response to stalled transcription. Defects in NER cause three distinct human diseases: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Each of these syndromes is characterized by premature onset of pathologies that overlap with those associated with old age in humans. This reveals the contribution of DNA damage to multiple agerelated diseases. Tissues affected include the skin, eye, bone marrow, nervous system and endocrine axis. This review emphasizes accelerated aging associated with xeroderma pigmentosum and discusses the cause of these pathologies, either mutation accumulation or cell death as a consequence of failure to repair DNA damage.

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Cerebellar neurodegeneration in human hereditary DNA repair disorders

Cited by 40 publications

References 14 publications

Binding of Pigment Epithelium-derived Factor (PEDF) to Retinoblastoma Cells and Cerebellar Granule Neurons

Binding of Pigment Epithelium-derived Factor (PEDF) to Retinoblastoma Cells and Cerebellar Granule Neurons

Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

Tissue-specific accelerated aging in nucleotide excision repair deficiency

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