Abstract:
:It is necessary for the cell-cycle machinery of neurons to be suppressed to promote differentiation and maintenance of their terminally differentiated state. Reactivation of the cell cycle in response to neurotoxic insults leads to neuronal cell death and some cell-cycle-related proteins contribute to the process. p27 kip1 (p27), an inhibitor of cyclin-dependent kinases, prevents unwarranted cyclin-dependent kinase activation. In this study, we have elucidated a novel mechanism via which p27 promotes apoptosis of neurons stimulated by neurotoxic amyloid peptide Aβ42 (Amyloid β1-42 peptide). Co-immunoprecipitation analysis revealed that p27 promotes interaction between Cyclin-dependent kinase 5 (Cdk5) and cyclin D1, which is induced by Aβ42 in cortical neurons. As a result, Cdk5 is sequestered from its neuronal activator p35 resulting in kinase deactivation. The depletion of p27, which was achieved by specific siRNA, restored Cdk5/p35 interaction by preventing association between Cdk5 and cyclin D1 and also abrogated Aβ42 induced apoptosis of cortical neurons. Furthermore, analysis of cell cycle markers suggested that p27 may play a role in Aβ42 induced aberrant cell cycle progression of neurons, which may result in apoptosis. These findings provide novel insights into how p27, which otherwise performs important neuronal functions, may become deleterious to neurons under neurotoxic conditions.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Jaiswal S,Sharma Pdoi
10.1111/jnc.13918subject
Has Abstractpub_date
2017-02-01 00:00:00pages
576-588issue
4eissn
0022-3042issn
1471-4159journal_volume
140pub_type
杂志文章abstract::The potential anxiolytic effects of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor subgroup 2 (mGluR₂) were investigated using a self-referencing recording technique with enzyme-based microelectrode arrays (MEAs) that reliably measures tonic and phasic changes in extracellular gluta...
journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1991-02-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1997-09-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb04676.x
更新日期:1981-11-01 00:00:00
abstract::Although pharmacological stimulation of a wide variety of transmitter receptors triggers phosphoinositide (PI) turnover, little is known about the type of synaptic activity required to activate this system. To investigate this question, we have used primary cultures of embryonic cortical neurons, which develop functio...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb10130.x
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1980.tb07870.x
更新日期:1980-11-01 00:00:00
abstract::Previous studies from this laboratory have shown that synthesis of GT3, the precursor of c series gangliosides, occurs in proximal Golgi compartments, as has been shown for the synthesis of GM3 and GD3, the precursors of a and b series gangliosides, respectively. In this work we studied whether the synthesis of GM3, G...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14935
更新日期:2020-04-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2007-03-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
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更新日期:2016-12-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1986-03-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2013-03-01 00:00:00
abstract::The aim of this study was to investigate the effect of long-term treatment with interferon (IFN)-alpha on the noradrenaline transporter of bovine adrenal medullary cells. Treatment of cultured adrenal medullary cells with IFN-alpha caused a decrease in uptake of [3H]noradrenaline by the cells in time (4-48 h)- and con...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1998.70041441.x
更新日期:1998-04-01 00:00:00
abstract::The myelin transcription factor 1 (Myt1) gene family is comprised of three zinc finger genes [Myt1, Myt1L (Myt1-Like) and NZF3] of the structurally unique CCHHC class that are expressed predominantly in the developing CNS. To understand the mechanism by which this family regulates neural differentiation, we searched f...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2005-06-01 00:00:00