DNA damage and neurodegenerative phenotypes in aged Ciz1 null mice.
DNA damage and neurodegenerative phenotypes in aged Ciz1 null mice.
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DOI：
10.1016/j.neurobiolaging.2017.10.014
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发表时间：
2018-03
影响因子：
4.2
通讯作者：
LeDoux MS
中科院分区：
文献类型：
--
作者：
Khan MM;Xiao J;Patel D;LeDoux MS
Cell-cycle dysfunction and faulty DNA repair are closely intertwined pathobiological processes that may contribute to several neurodegenerative disorders. CDKN1A interacting zinc finger protein 1 (CIZ1) plays a critical role in DNA replication and cell-cycle progression at the G1/S checkpoint. Germline or somatic variants in CIZ1 have been linked to several neural and extra-neural diseases. Recently, we showed that germline knock-out (KO) of Ciz1 is associated with motor and hematological abnormalities in young adult mice. However, the effects of CIZ1 deficiency in much older mice may be more relevant to understanding age-related declines in cognitive and motor functioning and age-related neurological disorders such as isolated dystonia and Alzheimer disease. Mouse embryonic fibroblasts from Ciz1−/− mice showed abnormal sensitivity to the effects of γ-irradiation with persistent DNA breaks, aberrant cell-cycle progression, and apoptosis. Aged (18-mo-old) Ciz1−/− mice exhibited marked deficits in motor and cognitive functioning, and, in brain tissues, overt DNA damage, NF-κB upregulation, oxidative stress, vascular dysfunction, inflammation, and cell death. These findings indicate that the deleterious effects of CIZ1 deficiency become more pronounced with aging and suggest that defects of cell-cycle control and associated DNA repair pathways in post-mitotic neurons could contribute to global neurological decline in elderly human populations. Accordingly, the G1/S cell-cycle checkpoint and associated DNA repair pathways may be targets for the prevention and treatment of age-related neurodegenerative processes.
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DOI：
10.1016/j.jalz.2016.03.004
发表时间：
2016-06
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Graff-Radford NR;Besser LM;Crook JE;Kukull WA;Dickson DW
通讯作者：
Dickson DW
影响因子：
3.6
作者：
Gellhaar, Sandra;Sunnemark, Dan;Galter, Dagmar
通讯作者：
Galter, Dagmar
影响因子：
64.8
作者：
Friedberg, EC
通讯作者：
Friedberg, EC
影响因子：
5.3
作者：
Borgesius, Nils Z.;de Waard, Monique C.;Elgersma, Ype
通讯作者：
Elgersma, Ype
影响因子：
5.3
作者：
Caccamo, Antonella;De Pinto, Vito;Oddo, Salvatore
通讯作者：
Oddo, Salvatore