scholarly journals Chromosome Instability, Aging and Brain Diseases

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1256
Author(s):  
Ivan Y. Iourov ◽  
Yuri B. Yurov ◽  
Svetlana G. Vorsanova ◽  
Sergei I. Kutsev
Keyword(s):  
Brain Aging ◽  
Chromosome Instability ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Accelerated Aging ◽  
Brain Diseases ◽  
Aging Brain ◽  
Ontogenetic Changes ◽  
Health And Disease

Chromosome instability (CIN) has been repeatedly associated with aging and progeroid phenotypes. Moreover, brain-specific CIN seems to be an important element of pathogenic cascades leading to neurodegeneration in late adulthood. Alternatively, CIN and aneuploidy (chromosomal loss/gain) syndromes exhibit accelerated aging phenotypes. Molecularly, cellular senescence, which seems to be mediated by CIN and aneuploidy, is likely to contribute to brain aging in health and disease. However, there is no consensus about the occurrence of CIN in the aging brain. As a result, the role of CIN/somatic aneuploidy in normal and pathological brain aging is a matter of debate. Still, taking into account the effects of CIN on cellular homeostasis, the possibility of involvement in brain aging is highly likely. More importantly, the CIN contribution to neuronal cell death may be responsible for neurodegeneration and the aging-related deterioration of the brain. The loss of CIN-affected neurons probably underlies the contradiction between reports addressing ontogenetic changes of karyotypes within the aged brain. In future studies, the combination of single-cell visualization and whole-genome techniques with systems biology methods would certainly define the intrinsic role of CIN in the aging of the normal and diseased brain.

The role of nitric oxide and PARP in neuronal cell death

2005 ◽  
pp. 146-156
Author(s):  
Mika Shimoji ◽  
Valina L. Dawson ◽  
Ted M. Dawson
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals Microglial TonEBP mediates LPS-induced inflammation and memory loss as transcriptional cofactor for NF-κB and AP-1

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Gyu Won Jeong ◽  
Hwan Hee Lee ◽  
Whaseon Lee-Kwon ◽  
Hyug Moo Kwon
Keyword(s):  
Microglial Activation ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Myeloid Cells ◽  
Memory Loss ◽  
Neuronal Cell ◽  
Microglial Cell Line ◽  
Bv2 Cells ◽  
Pro Inflammatory Cytokines

Abstract Background Microglia are brain-resident myeloid cells involved in the innate immune response and a variety of neurodegenerative diseases. In macrophages, TonEBP is a transcriptional cofactor of NF-κB which stimulates the transcription of pro-inflammatory genes in response to LPS. Here, we examined the role of microglial TonEBP. Methods We used microglial cell line, BV2 cells. TonEBP was knocked down using lentiviral transduction of shRNA. In animals, TonEBP was deleted from myeloid cells using a line of mouse with floxed TonEBP. Cerulenin was used to block the NF-κB cofactor function of TonEBP. Results TonEBP deficiency blocked the LPS-induced expression of pro-inflammatory cytokines and enzymes in association with decreased activity of NF-κB in BV2 cells. We found that there was also a decreased activity of AP-1 and that TonEBP was a transcriptional cofactor of AP-1 as well as NF-κB. Interestingly, we found that myeloid-specific TonEBP deletion blocked the LPS-induced microglia activation and subsequent neuronal cell death and memory loss. Cerulenin disrupted the assembly of the TonEBP/NF-κB/AP-1/p300 complex and suppressed the LPS-induced microglial activation and the neuronal damages in animals. Conclusions TonEBP is a key mediator of microglial activation and neuroinflammation relevant to neuronal damage. Cerulenin is an effective blocker of the TonEBP actions.

scholarly journals The Mitotic Apparatus and Kinetochores in Microcephaly and Neurodevelopmental Diseases

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 49 ◽  
Author(s):  
Francesca Degrassi ◽  
Michela Damizia ◽  
Patrizia Lavia
Keyword(s):  
Chromosome Instability ◽  
Critical Role ◽  
Somatic Cells ◽  
Neuronal Cell ◽  
Mitotic Division ◽  
Special Focus ◽  
Mitotic Apparatus ◽  
Genes Encoding ◽  
Congenital Microcephaly

Regulators of mitotic division, when dysfunctional or expressed in a deregulated manner (over- or underexpressed) in somatic cells, cause chromosome instability, which is a predisposing condition to cancer that is associated with unrestricted proliferation. Genes encoding mitotic regulators are growingly implicated in neurodevelopmental diseases. Here, we briefly summarize existing knowledge on how microcephaly-related mitotic genes operate in the control of chromosome segregation during mitosis in somatic cells, with a special focus on the role of kinetochore factors. Then, we review evidence implicating mitotic apparatus- and kinetochore-resident factors in the origin of congenital microcephaly. We discuss data emerging from these works, which suggest a critical role of correct mitotic division in controlling neuronal cell proliferation and shaping the architecture of the central nervous system.

scholarly journals Role of microglial IKKβ in kainic acid-induced hippocampal neuronal cell death

Brain ◽  
2008 ◽  
Vol 131 (11) ◽  
pp. 3019-3033 ◽  
Author(s):  
Ik-Hyun Cho ◽  
Jinpyo Hong ◽  
Eun Cheng Suh ◽  
Jae Hwan Kim ◽  
Hyunkyoung Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Kainic Acid ◽  
Neuronal Cell Death ◽  
Neuronal Cell
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