p27 small interfering RNA induces cell death through elevating cell cycle activity in cultured cortical neurons: a proof-of-concept study

Akashiba, Hiroki; Matsuki, Naoaki; Nishiyama, N.

doi:10.1007/s00018-006-6194-4

Cited by 21 publications

(9 citation statements)

References 34 publications

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“…To further examine whether p27 is required for Cux1 to regulate dendritic morphology, we constructed two RNAi constructs for p27, p27-RNAiA and p27-RNAiB, which were reported to be effective [20], [21], and transfected them into cultured cortical pyramidal neurons. Both of them decreased the dendritic complexity (Figure 5C–D).…”

Section: Resultsmentioning

confidence: 99%

The Transcription Factor Cux1 Regulates Dendritic Morphology of Cortical Pyramidal Neurons

Zhao

Wang

et al. 2010

PLoS ONE

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In the murine cerebral cortex, mammalian homologues of the Cux family transcription factors, Cux1 and Cux2, have been identified as restricted molecular markers for the upper layer (II-IV) pyramidal neurons. However, their functions in cortical development are largely unknown. Here we report that increasing the intracellular level of Cux1, but not Cux2, reduced the dendritic complexity of cultured cortical pyramidal neurons. Consistently, reducing the expression of Cux1 promoted the dendritic arborization in these pyramidal neurons. This effect required the existence of the DNA-binding domains, hence the transcriptional passive repression activity of Cux1. Analysis of downstream signals suggested that Cux1 regulates dendrite development primarily through suppressing the expression of the cyclin-dependent kinase inhibitor p27Kip1, and RhoA may mediate the regulation of dendritic complexity by Cux1 and p27. Thus, Cux1 functions as a negative regulator of dendritic complexity for cortical pyramidal neurons.

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Section: Resultsmentioning

confidence: 99%

The Transcription Factor Cux1 Regulates Dendritic Morphology of Cortical Pyramidal Neurons

Zhao

Wang

et al. 2010

PLoS ONE

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“…The endogenous inhibitors include 2 subclasses: 1) the Ink4 family (including p16 Ink4a , p15 Ink4b , p18 Ink4c , and p19 Ink4d ) and the Cip/Kip family (including p21 Cip1 , p27 Kip1 and p57 Kip2 ) [2, 26, 31]. P27 is highly expressed in neurons [32]. Studies in the retina and other tissues indicate that Ink4 proteins are specific for CDK4 and CDK6 and prevent the formation with cyclin D, whereas Cip/Kip molecules broadly and nonspecifically block activity of CDKs [26, 33].…”

Section: Cell Cycle Pathways and Mechanismsmentioning

confidence: 99%

“…The endogenous CDK inhibitor p27 protein expression declines to an undetectable level after a 24-h application of etoposide in primary neuronal cultures, returning nearly back basal level following treatment with cell cycle inhibitors [32]. After 24-h transfection of p27 siRNA, p27 protein expression is down-regulated and accompanied by an increase in BrdU uptake into neurons, as well as Rb phosphorylation.…”

Section: Cdk Inhibitors As Therapeutic Targets In Cns Insultsmentioning

confidence: 99%

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Cell Cycle Activation and Spinal Cord Injury

Stoica

Faden

2011

Neurotherapeutics

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Summary Traumatic spinal cord injury (SCI) evokes a complex cascade of events with initial mechanical damage leading to secondary injury processes that contribute to further tissue loss and functional impairment. Growing evidence suggests that the cell cycle is activated following SCI. Up-regulation of cell cycle proteins after injury appears to contribute not only to apoptotic cell death of postmitotic cells, including neurons and oligodendrocytes, but also to post-traumatic gliosis and microglial activation. Inhibition of key cell cycle regulatory pathways reduces injury-induced cell death, as well as microglial and astroglial proliferation both in vitro and in vivo. Treatment with cell cycle inhibitors in rodent SCI models prevents neuronal cell death and reduces inflammation, as well as the surrounding glial scar, resulting in markedly reduced lesion volumes and improved motor recovery. Here we review the effects of SCI on cell cycle pathways, as well as the therapeutic potential and mechanism of action of cell cycle inhibitors for this disorder.

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“…It is demonstrated that reduced expression of endogenous p27 induced cell death in cultured cortical neurons by transfection of p27 small interfering RNA (siRNA) [111]. p27 may alleviate KA-induced seizure and hippocampal degeneration [112].…”

Section: Potentials Of Antiglutamate Excitotoxicity As a Therapeutmentioning

confidence: 99%

Kainic Acid‐Induced Neurodegenerative Model: Potentials and Limitations

Zheng

Zhang

Luo

et al. 2010

BioMed Research International

118

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Excitotoxicity is considered to be an important mechanism involved in various neurodegenerative diseases in the central nervous system (CNS) such as Alzheimer's disease (AD). However, the mechanism by which excitotoxicity is implicated in neurodegenerative disorders remains unclear. Kainic acid (KA) is an epileptogenic and neuroexcitotoxic agent by acting on specific kainate receptors (KARs) in the CNS. KA has been extensively used as a specific agonist for ionotrophic glutamate receptors (iGluRs), for example, KARs, to mimic glutamate excitotoxicity in neurodegenerative models as well as to distinguish other iGluRs such as α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors and N-methyl-D-aspartate receptors. Given the current knowledge of excitotoxicity in neurodegeneration, interventions targeted at modulating excitotoxicity are promising in terms of dealing with neurodegenerative disorders. This paper summarizes the up-to-date knowledge of neurodegenerative studies based on KA-induced animal model, with emphasis on its potentials and limitations.

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p27 small interfering RNA induces cell death through elevating cell cycle activity in cultured cortical neurons: a proof-of-concept study

Cited by 21 publications

References 34 publications

The Transcription Factor Cux1 Regulates Dendritic Morphology of Cortical Pyramidal Neurons

The Transcription Factor Cux1 Regulates Dendritic Morphology of Cortical Pyramidal Neurons

Cell Cycle Activation and Spinal Cord Injury

Kainic Acid‐Induced Neurodegenerative Model: Potentials and Limitations

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