Cyclin-dependent Kinase 5 in Lewy Body-like Inclusions in Anterior Horn Cells of a Patient with Sporadic Amyotrophic Lateral Sclerosis

Nakamura, S.; Kawamoto, Yuko; Nakano, Satoshi; Ikemoto, Akito; Akiguchi, Ichiro; Kimura, Jun

doi:10.1212/wnl.48.1.267

Cited by 48 publications

(19 citation statements)

References 4 publications

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“…Increased p53 and pRb staining have been reported (36,41,42) as well as regulators of pRb activity, the cyclin-dependent kinases and their inhibitors (3,6,37,43). Cyclin-dependent kinases, pRb, and E2F activity have been implicated in β-amyloid toxicity in an in vitro model of Alzheimer's disease (18,19).…”

Section: Discussionmentioning

confidence: 99%

Response of Cell Cycle Proteins to Neurotrophic Factor and Chemokine Stimulation in Human Neuroglia

Jordan‐Sciutto

Fenner

Wiley

et al. 2001

Experimental Neurology

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Increased expression of neurotrophins (e.g., NGF, BDNF) and chemokines (e.g., RANTES) has been observed in neurodegenerative diseases. We examined the effect of these factors on intracellular signaling cascades inducing cell cycle proteins p53, pRb, and E2F1 in human fetal mixed neuronal and glial cells. Comparing neurotrophin-and chemokine-treated cultures with untreated controls showed altered subcellular localization and expression of hyperphosphorylated retinoblastoma protein (ppRb), E2F1, and p53. Using immunofluorescent laser confocal microscopy, E2F1 and ppRb were detected exclusively in neuronal nuclei in control cultures while p53 was cytoplasmic in astrocytes and nuclear in neurons. Following treatment with neurotrophins, E2F1 and ppRb were observed in the cytoplasm of neurons, while p53 was observed in both neuronal and astrocytic nuclei. Similar findings were observed following treatment with RANTES. Semiquantitative analysis using immunoblots showed an increase in the amount of phosphorylated pRb in treated cultures. Induction of cell cycle proteins may play a role in neurodegeneration associated with neurotrophin and chemokine stimulation.

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Section: Discussionmentioning

confidence: 99%

Response of Cell Cycle Proteins to Neurotrophic Factor and Chemokine Stimulation in Human Neuroglia

Jordan‐Sciutto

Fenner

Wiley

et al. 2001

Experimental Neurology

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“…Cdk5 is involved in cytoskeletal protein phosphorylation and may lead to NF-tangle formation, a critical change associated with neurodegenerative diseases (Mandelkow et al, 1992;Baumann et al, 1993;Nakamura et al, 1997;Julien and Mushynski, 1998;Bajaj et al, 1999). A comparative study of the phosphorylation status of cytoskeletal elements shown previously to be phosphorylated by Cdk5 was performed with SMI-31 antibody.…”

Section: Aberrant Phosphorylation Of the Cytoskeleton In Cdk5 Null MImentioning

confidence: 99%

Neuronal Cyclin-Dependent Kinase 5 Activity Is Critical for Survival

Tanaka

Veeranna²,

Ohshima

et al. 2001

J. Neurosci.

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Cyclin-dependent kinase 5 (Cdk5) null mice exhibit a unique phenotype characterized by perinatal mortality, disrupted cerebral cortical layering attributable to abnormal neuronal migration, lack of cerebellar foliation, and chromatolytic changes of neurons in the brainstem and the spinal cord. Because Cdk5 is expressed in both neurons and astrocytes, it has been unclear whether this phenotype is primarily attributable to defects in neurons or in astrocytes. Herein we report reconstitution of Cdk5 expression in neurons in Cdk5 null mice and its effect on the null phenotype. Unlike the Cdk5 null mice, the reconstituted Cdk5 null mice that express the Cdk5 transgene under the p35 promoter (TgKO mice) were viable and fertile. Because Cdk5 expression is mainly limited to neurons in these mice and rescues the defects in the nervous system of the Cdk5 null phenotype, it clearly demonstrates that Cdk5 activity is necessary for normal development and survival of p35-expressing neurons.

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“…As phosphorylation of cytoskeletal proteins is involved in cytoskeletal dynamics during active process extension of differentiating neurons, Cdk5 has been implicated in neurite extension, neuronal migration, and neuronal differentiation (Nikolic et al, 1996). In neurodegenerative diseases, Cdk5 participates in the hyperphosphorylation of the Lewy bodies of Parkinson's disease (Brion and Couck, 1995), Lewy bodylike inclusions of amyotrophic lateral sclerosis (Nakamura et al, 1997), and neuro brillary tangles of Alzheimer's disease (Paudel et al, 1993).…”

Section: Dk5mentioning

confidence: 99%

Expression and localization of cyclin-dependent kinase 5 in apoptotic human glioma cells

Catania¹

2001

Neuro-Oncology

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Neuro-Oncology nA P R I L 2 0 0 1 89 Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, is expressed predominately in mature neurons and is implicated in neurite extension, neuronal migration, and neuronal differentiation. Cdk5 protein expression also has been associated with apoptosis in a number of nonneuronal model systems. In normal brain, substrates for Cdk5 include neuro lament and tau proteins. Because human tumors of glial origin can express neuronal proteins, we examined whether Cdk5 and its activator protein, P35, are present in early passage human glioblastoma multiforme (GBM) cells lines and primary tumor specimens. Here we report the expression of Cdk5 and an "active" proteolytic form of P35 in human GBM cells and demonstrate kinase activity of the holoenzyme. We also show that Cdk5 kinase activity and expression of its activator protein, P35, is increased in the human GBM cell line M059J after exposure to ionizing radiation and that P35 is localized within M059J cells undergoing apoptosis. These results suggest a possible role for Cdk5 in mediating apoptosis in human GBM cells. Neuro-Oncology 3, 89-98, 2001 (Posted to Neuro-Oncology [serial online], Doc. 00-038, February 15, 2001

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Cyclin-dependent Kinase 5 in Lewy Body-like Inclusions in Anterior Horn Cells of a Patient with Sporadic Amyotrophic Lateral Sclerosis

Cited by 48 publications

References 4 publications

Response of Cell Cycle Proteins to Neurotrophic Factor and Chemokine Stimulation in Human Neuroglia

Response of Cell Cycle Proteins to Neurotrophic Factor and Chemokine Stimulation in Human Neuroglia

Neuronal Cyclin-Dependent Kinase 5 Activity Is Critical for Survival

Expression and localization of cyclin-dependent kinase 5 in apoptotic human glioma cells

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