Wyniki wyszukiwania

1

Ceramides and sphingosine-1-phosphate in molecular mechanisms of neuronal cell death

100%

Czubowicz K., Strosznajder R. P.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Ceramides, bioactive members of the sphingolipids can be generated by de novo synthesis, sphingomyelin hydrolysis and by acylation of sphingosine. Ceramides are known to regulate several cellular processes, including differentiation, growth suppression, cell senescence and apoptosis. The ceramide levels increased in several pathological conditions such as brain ischemia, hypoglycemia, inflammation and in neurodegenerative disorders. Sphingosine, a metabolite of ceramide is phosphorylated by sphingosine kinases (Sphk type 1and 2) to sphingosine-1-phosphate (S1P). Sphingosine kinases are critical regulators of the sphingolipid biostat. The aim of this study was to investigate the role of ceramide and S1P in molecular mechanisms of neuronal cells death. The human neuroblastoma cell line (SH-SY5Y) was exposed to cell-permeable C2-ceramide. Ceramide decreased the viability of SH-SY5Y cells in concentration dependent manner. The intracellular free radical generation after ceramide treatment was about 3-fold higher comparing to control. Concomitantly our study indicated that ceramide induced poly(ADP-ribose) polymerase-1 (PARP-1) activation and decreased the level of apoptosis inducing factor (AIF) in mitochondria. Ceramide diminished the expression and level of anti-apoptotic Bcl-2 protein. PARP-1 inhibitor enhanced the level of Bcl-2 protein and cells survival keeping the level of AIF in mitochondria unchanged. The recent studies indicated that ERK1/2 are involved directly in regulation of PARP-1 activity. The specific inhibitor of these kinases protected cells against death evoked by ceramide in our experimental conditions. Moreover, our study indicated, that sphingosine-1-phosphate (S1P) increased Bcl-2 gene expression and SH-SY5Y cells survival after ceramide treatment. Summarizing, our data present that PARP-1 inhibitor and sphingosine-1-phosphate (S1P) through modulation of anti-apoptotic proteins protect mitochondria and neuronal cells against death evoked by ceramide. Supported by statutory budget of MRC and NCN Grant 5870/PO1/2011/40

2

High-throughput assays for measuring oxidative stress and mitochondrial dysfunction in neuronal cell cultures

100%

Krzemien J., Jacobsson S.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Drugs of abuse may cause acute as well as chronic damage to the nervous system, and a common mechanism of neurotoxicity is to induce disturbances in mitochondrial function. The mitochondrion is also an important source for cytotoxic reactive oxygen species (ROS). If the mitochondrial membrane potential (MMP) becomes depolarized, it can increase the production of ROS. This project has evaluated whether the fluorophore JC-1, which measures the depolarization of MMP, and the fluorophore H2DCFDA that oxidizes and produce fluorescence in the presence of oxygen radicals, are useful tools to screen for drug-induced neurotoxicity. The studies have been performed in embryonal carcinoma (EC) P19 cells that are pluripotent and upon retinoic acid (RA)-treatment will differentiate in culture into neurons, astrocytes and oligodendrocytes. In order to determine the predictive validity of the model/methods, a number of compounds known to cause oxidative stress and mitochondrial dysfunction have been examined (hydrogen peroxide, ionomycin, sodium azide). Main techniques employed culturing, induction and differentiation of neuronal cells, pharmacological dose-response experiments, detection and quantification of fluorescence using microplate reader and fluorescence microscopy, microplate-based colorimetric methods for assessment of cell viability, pharmacological/toxicological data and statistical analyses using the GraphPad prism software.

3

Caspase and calpain mediated proteolysis of nonerythroid spectrin subunits in neuronal cells undergoing apaptosis

100%

Wang K. K. W., Rathna N., Rand P., McGinnis K., Glantz S. B., Morrow J. S.

Cellular and Molecular Biology Letters

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1998

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tom 03

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nr 2

4

Dynamics of human CDK2 and CDK5 studied by computer simulations

100%

Otyepka M., Bartova I., Kriz Z., Koca J.

Cellular and Molecular Biology Letters

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2005

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tom 10

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nr Suppl.2

5

Distribution of some neuropeptides in the porcine inferior mesenteric ganglion

100%

Lakomy M., Happola O., Majewski M., Wasowicz K.

Folia Histochemica et Cytobiologica

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1996

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tom 34

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nr 2

6

Association of ecto-5'-nucleotidase activity and erbB-2 receptor function

100%

Rosi F., Tabucchi A., Carlucci F., Marinello E., Cinci G., Zanoni L.

Cellular and Molecular Biology Letters

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1999

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tom 04

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nr 3

7

Influence of fixation and histological procedure on the morphometric parameters of neuronal cells

100%

Sadowski M., Morys J., Berdel B., Maciejewska B.

Folia Morphologica

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1995

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tom 54

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nr 4

8

Developmental regulation of Ubc9 in the rat nervous system

84%

Watanabe M., Takahashi K., Tomizawa K., Mizusawa H., Takahashi H.

Acta Biochimica Polonica

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2008

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tom 55

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nr 4

681-686

The SUMO-conjugating enzyme Ubc9 is an essential enzyme in the SUMO (small ubiquitin-related modifier) protein modification system. Although sumoylation, covalent modification of cellular proteins by SUMO, is considered to regulate various cellular processes, and many substrates for sumoylation have been identified recently, the regulation of Ubc9 expression has not been examined in detail. We analyzed the expression of Ubc9 during rat brain development at the mRNA and protein levels. Northern and Western blot analyses revealed that expression of Ubc9 and SUMO-1 was developmentally regulated, while that of the ubiquitin-conjugating enzyme UbcH7 did not change so dramatically. In situ hybridization analysis revealed that the expression of Ubc9 was high in neuronal stem cells and moderate in differentiated neurons at embryonic stages. In the adult brain, moderate expression was observed in subsets of neurons, such as the dentate granular neurons and pyramidal neurons in the hippocampal formation and the large pyramidal neurons in the cerebral cortex. These results suggest that the Ubc9-SUMO system might participate in the proliferation and differentiation of neuronal cells in the developing brain and in neuronal plasticity in the adult brain.

9

The evaluation of the role of mGluR7 in neuronal apoptotic processes by usage of AMN082, a selective mGluR7 agonist and mGluR7 knockout-derived cells

84%

Jantas D., Lech T., Pilc A., Lason W.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Increasing body of evidence suggests a neuroprotective potential of metabotropic glutamatergic receptor group III (mGluR III) stimulation, however the role of particular subtypes of these receptors (mGluR4, mGluR7, mGluR8) in apoptotic processes is not fully recognized. Of special interest is the study on the role of mGluR7 which is widely expressed throughout the brain and recently developed selective positive allosteric modulator of this receptor, AMN082 (N,N=-dibenzhydrylethane-1,2-diamine dihydrochloride) enables investigation the biological role of mGluR7. In the present study, firstly we evaluated the possible neuroprotective effects of AMN082 (0.001–1 µM) on neurotoxicity induced by various apoptotic [stimuli staurosporine (St), doxorubicin (Dox) and low potassium (LP)] in 7 DIV cerebellar granule cells (CGC). The data showed that AMN082 (0.1–1 µM) partially attenuated the cell death induced by St and LP, but not by Dox. Next, we investigated the role of mGluR7 in neuronal cell death by testing the vulnerability of CGC from wild and mGluR7KO animals to toxic action of St, Dox and LP. No differences between groups under basal conditions have been found. However, after primary deprivation of CGC cells from potassium in culture medium and secondary application of proapoptotic stimuli we observed the higher vulnerability of mGluR7KO CGC to cell damaging effect of St and Dox but not LP. Further experiments performed on cortical glia cells demonstrated higher toxic action of St and Dox in mGluR7KO cells when compared to wild type one. Additionally, in mGluR7KO glia cells we found higher basal and stimulated by St or Dox caspase-3 activity when compared to wild type one. The obtained data suggest that specific stimulation of mGluR7 by AMN082 could be protective against staurosporine and low-potassium induced neuronal ell death. Moreover, the presence of mGluR7 could be particularly important for survival of glia cells under harmful conditions. The study was supported by statutory funds for Institute of Pharmacology PAS and grant No NN405611638 from the Ministry of Science and Higher Education, Warsaw, Poland.

10

Repeated isoflurane exposures of neonatal rats contribute to cognitive dysfunction in juvenile animals: the role of miR-497 in isoflurane-induced neurotoxicity

84%

Que Y., Zhang F., Peng J., Zhang Z., Zhang D., He M.

Folia Histochemica et Cytobiologica

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2021

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tom 59

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nr 2

11

Underlying mechanism of regulatory actions of diclofenac, a nonsteroidal anti-inflammatory agent, on neuronal potassium channels and firing: an experimental and theoretical study

84%

Huang C. W., Hung T. Y., Liao Y. K., Hsu M. C., Wu S. N.

Journal of Physiology and Pharmacology

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2013

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tom 64

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nr 3

12

Evidence for state-dependent block of DPI 201-106, a synthetic inhibitor of Na+ channel inactivation, on delayed-rectifier K+ current in pituitary tumor (GH3) cells

84%

Wang Y.-J., Lin M.-W., Lin A.-A., Peng H., Wu S.-N.

Journal of Physiology and Pharmacology

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2008

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tom 59

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nr 3

409-423

DPI 201-107 (DPI), a diphenylpiperazinylindole derivative, was reported to be a cardio-selective modifier of voltage-gated Na+ channels. It remains unclear whether DPI has any effects on ion currents. The effects of DPI on ion currents and membrane potential in pituitary tumor (GH3) cells were investigated in this study. DPI (1-100 µM) suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in a concentration-dependent manner with an IC50 value of 9.4 µM. The presence of DPI also enhanced the rate and extent of IK(DR) inactivation. Recovery from block by DPI (10 µM) was fitted by a single exponential. Crossover of tail currents during the exposure to DPI was also observed. Under current-clamp recordings, DPI prolonged action potential duration in GH3 cells. With a minimal binding scheme, DPI-induced block of IK(DR) was quantitatively provided. The exposure to DPI also blocked IK(DR) with a concomitant increase in current inactivation in NG108-15 neuronal cells. Taken together, the results imply that DPI acts as an open-channel blocker of delayed-rectifier K+ channels in these cells. The widening of action potentials induced by DPI in these cells may be explained mainly by its block of IK(DR) in a state-dependent manner.

13

Signals mediating Klotho-induced neuroprotection in hippocampal neuronal cells

84%

Cheng M.-F., Chen L.-J., Niu H.-S., Yang T.-T., Lin K.-C., Cheng J.-T.

Acta Neurobiologiae Experimentalis

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2015

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tom 75

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nr 1

The erythropoietin (Epo) receptor (EpoR) is expressed in the brain and was shown to have neuroprotective effects against brain damage in animal models. A recent study indicated that EpoR and its activity are the downstream effectors of Klotho for cytoprotection in the kidney. Thus, we propose that Klotho can stimulate the expression of EpoR in neuronal cells to enhance Epo-mediated protection. H19-7 hippocampal neuronal cells were treated with recombinant Klotho. In H19-7 cells, Klotho increased the expression of both the EpoR protein and mRNA. Klotho also enhanced the transcription activity of the EpoR promoter in H19-7 cells. Moreover, Klotho augmented the Epo-triggered phosphorylation of Jak2 and Stat5 and protected H19-7 cells from hydrogen peroxide cytotoxicity. The silencing of EpoR abolished the protective effect of Klotho against peroxide-induced cytotoxicity. Finally, the silencing of GATA1 diminished the Klotho-induced increase in EpoR protein and mRNA expression as well as its promoter activity. In conclusion, Klotho increased EpoR expression in neuronal cells through GATA1, thereby enabling EpoR to function as a cytoprotective protein against oxidative injury.

14

Differentiated Paju cells have increased resistance to toxic effects of potassium ionophores

84%

Teplova V., Jaaskelainen E., Salkinoja-Salonen M., Saris N. E. L., Serlachius M., Li F. Y., Andersson L. C.

Acta Biochimica Polonica

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2004

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tom 51

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nr 2

In this study we have investigated the impact of differentiation of neuronal cells on their sensitivity to microbial toxins. We used the human neural crest-derived tumor cell line Paju, which can be induced to differentiation in vitro by treatment with phorbol 12-myristate 13-acetate. Addition of the highly toxic potassium ionophores cereulide (4.5 and 9.0 ng/ml) or valinomycin (20 ng/ml), to cultures of undifferentiated Paju cells caused collapse of the mitochondrial membrane potential — measured with the fluorescent probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetrabenzimidazole carbo- cyanine iodide (JC-1) followed by detachment of the cells and their apoptotic death. After induced differentiation of the Paju cells, their mitochondria retained the membrane potential upon exposure to the toxins and the cells displayed increased resistance to apoptosis as compared with undifferentiated cells. This effect may be caused by an elevated expression of the anti-apoptotic protein Bcl-2 and of the neuroprotective factor, stanniocalcin, in differentiated cells.

15

Does senile impairment of cholinergic system in rats concern only disturbances in cholinergic phenotype or the progressive degeneration of neuronal cell bodies?

84%

Niewiadomska G., Wyrzykowska J., Chechlacz M.

Acta Biochimica Polonica

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2000

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tom 47

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nr 2

The trophic effect of continuous intraventricular infusion of nerve growth factor (NGF) on morphology of the basal forebrain (BF) cholinergic neurons was tested in 4- and 28-month-old male Wistar rats. All studies were conducted using behaviorally uncharacterized animals from the same breeding colony. Immunohistochemical procedure for choline acetyltransferase (ChAT) and p75NTR receptor has been applied to identify cholinergic cells in the structures of basal forebrain (BF). Using a quantitative image analyzer, morphometric and densitometric parameters of ChAT- and p75NTR-positive cells were measured immediately after cessation of NGF infusion. In 28-month-old non-treated rats the number of intensively ChAT-positive cells in all forebrain structures was reduced by 50-70% as compared with young animals. The remaining ChAT-positive cells appeared shrunken and the neuropil staining was markedly reduced. In contrast, the same neurons when stained for p75NTR were numerous and distinctly visible with perfect morphology. Analysis of Nissl stained sections also showed that 28-month-old rats did not display significant losses of neuronal cell bodies. NGF restored the number of intensely stained ChAT-positive cells to about 90% of that for young controls and caused a significant increase in size of those cells in 28-month-old rats as compared with the control, age-matched group. NGF did not influence the morphology of p75NTR-positive neurons, which were well labeled, irrespective of treatment and age of the rats. In 4-month-old rats, NGF infusion decreased the intensity of both ChAT and p75NTR immunostaining. These data provide some evidence for preservation of BF cholinergic neurons from atrophy during aging and indicate that senile impairment of the cholinergic system in rats concerns decrease in ChAT-protein expression rather than an acute degeneration of neuronal cell bodies. Treatment with NGF resulted in restoration of cholinergic phenotype in the BF neurons of aged rats. However, the present study also rises issue of possible detrimental effects of NGF in young normal animals.

16

Mouse embryonic stem cell differentiation and loss os function analysis in vitro

84%

Wobus A. M., Rohwedel J., Kaomei G., Fassler R.

Folia Histochemica et Cytobiologica. Supplement

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1997

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tom 35

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nr 2

17

Neuronal cyclin-dependent kinase 5 [cdk5] and its specific inhibitor [CIP]: its physiological and pathological role in the nervous system

84%

Zheng Y., Kesavapany S., Pant H. C.

Cellular and Molecular Biology Letters

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2003

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tom 08

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nr 2A

18

Extracellular ATP as a neurotransmitter: its role in synaptic plasticity in the hippocampus

84%

Wieraszko A.

Acta Neurobiologiae Experimentalis

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1996

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tom 56

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nr 2

19

A proteomic analysis of the effect of MAPK pathway activation on L-glutamate-induced neuronal cell death

84%

Kang S., Kim E. Y., Bahn Y. J., Chung J. W., Lee D. H., Park S. G., Yoon T. S., Park B. C., Bae K. H.

Cellular and Molecular Biology Letters

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2007

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tom 12

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nr 1

Oxidative stress has been implicated in the pathogenesis of neuronal degenerative diseases. It is also widely known that oxidative stress induces mitogen-activated protein kinase (MAPK) signaling cascades. In this study, we used proteomic analysis to investigate the role of the MAPK pathway in oxidative stress-induced neuronal cell death. The results demonstrated that several proteins, including eukaryotic translation elongation factor 2 (eEF2) and enolase I, showed a differential expression pattern during the neuronal cell death process, and this was MAPK pathway dependent. Several chaperone and cytoskeletal proteins including heat shock protein 70, calreticulin, vimentin, prolyl 4-hydroxylase β polypeptide, and transgelin 2 were up-or down-regulated, despite their expressions not depending on the MAPK pathway. These findings strongly suggest that the expressions of proteins which play protective roles are independent of the MAPK pathway. On the other hand, eEF2 and enolase I may be the downstream targets of the MAPK pathway.

20

The two major protein isoforms of ankyrin 2 are differentially localized in Drosophila neurons

84%

Hortsch M., Paisley K. L., Tian M. Z., Qian M., Bouley M., Chandler R.

Cellular and Molecular Biology Letters

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2001

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tom 06

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nr 2

Ograniczanie wyników

Ceramides and sphingosine-1-phosphate in molecular mechanisms of neuronal cell death

High-throughput assays for measuring oxidative stress and mitochondrial dysfunction in neuronal cell cultures

Caspase and calpain mediated proteolysis of nonerythroid spectrin subunits in neuronal cells undergoing apaptosis

Dynamics of human CDK2 and CDK5 studied by computer simulations

Distribution of some neuropeptides in the porcine inferior mesenteric ganglion

Association of ecto-5'-nucleotidase activity and erbB-2 receptor function

Influence of fixation and histological procedure on the morphometric parameters of neuronal cells

Developmental regulation of Ubc9 in the rat nervous system

The evaluation of the role of mGluR7 in neuronal apoptotic processes by usage of AMN082, a selective mGluR7 agonist and mGluR7 knockout-derived cells

Repeated isoflurane exposures of neonatal rats contribute to cognitive dysfunction in juvenile animals: the role of miR-497 in isoflurane-induced neurotoxicity

Underlying mechanism of regulatory actions of diclofenac, a nonsteroidal anti-inflammatory agent, on neuronal potassium channels and firing: an experimental and theoretical study

Evidence for state-dependent block of DPI 201-106, a synthetic inhibitor of Na+ channel inactivation, on delayed-rectifier K+ current in pituitary tumor (GH3) cells

Signals mediating Klotho-induced neuroprotection in hippocampal neuronal cells

Differentiated Paju cells have increased resistance to toxic effects of potassium ionophores

Does senile impairment of cholinergic system in rats concern only disturbances in cholinergic phenotype or the progressive degeneration of neuronal cell bodies?

Mouse embryonic stem cell differentiation and loss os function analysis in vitro

Neuronal cyclin-dependent kinase 5 [cdk5] and its specific inhibitor [CIP]: its physiological and pathological role in the nervous system

Extracellular ATP as a neurotransmitter: its role in synaptic plasticity in the hippocampus

A proteomic analysis of the effect of MAPK pathway activation on L-glutamate-induced neuronal cell death

The two major protein isoforms of ankyrin 2 are differentially localized in Drosophila neurons