NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo.

Lone Dagø, Christian Bonde, Dan Peters, Arne Møller, Signe Farsø Bomholt, J Barbara P Hartz, Morten Meyer, Jørgen Drejer, Mette Grønborg

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2002-Apr
OriginalsprogEngelsk
TidsskriftJournal of Neurochemistry
Vol/bind81
Udgave nummer1
Sider (fra-til)17-24
Antal sider7
ISSN0022-3042
StatusUdgivet - 1. apr. 2002

Fingeraftryk

PC12 Cells
Nerve Growth Factor
Phosphorylation
Oximes
NS 1231
In Vitro Techniques
Gerbillinae
Middle Cerebral Artery Infarction
N-Methylaspartate
Neurons
Cell Death
Chemical activation
Binding Sites

Citer dette

Dagø, L., Bonde, C., Peters, D., Møller, A., Bomholt, S. F., Hartz, J. B. P., ... Grønborg, M. (2002). NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo. Journal of Neurochemistry, 81(1), 17-24.
Dagø, Lone ; Bonde, Christian ; Peters, Dan ; Møller, Arne ; Bomholt, Signe Farsø ; Hartz, J Barbara P ; Meyer, Morten ; Drejer, Jørgen ; Grønborg, Mette. / NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo. I: Journal of Neurochemistry. 2002 ; Bind 81, Nr. 1. s. 17-24.
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title = "NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo.",
abstract = "NS 1231 [5-(4-chlorophenyl)-6,7,8,9-tetrahydro-1H-pyrrolo-[3.2-h]naphthalene-2,3-dione-3-oxime] belongs to a chemical series of compounds, which exhibit neurotrophic-like activities. In vitro, NS 1231 rescued nerve growth factor (NGF)-differentiated PC12 cells from death induced by withdrawal of trophic factors. In addition, NS 1231 stimulated NGF-induced neurite outgrowth of undifferentiated PC12 cells. At the molecular level, NS 1231 enhanced NGF-induced signalling events, such as TrkA phosphorylation at the Shc-binding site Tyr490 as well as ERK activation in PC12 cells. Moreover, NS 1231 reduced NMDA-induced excitotoxicity in organotypic hippocampal slice cultures. In a gerbil model of transient global ischaemia, treatment with NS 1231 reduced the delayed loss of neurons in the hippocampal CA1 layer. Furthermore, NS 1231 treatment resulted in a 43{\%} reduction in total infarct volume in the mouse middle cerebral artery occlusion (MCAO) model. The present data thus implicate a therapeutic potential of NS 1231 or structural analogues in treatment of cerebral ischaemia.",
keywords = "Animals, Cell Survival, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Enzyme Activation, Gerbillinae, Hippocampus, Indoles, Infarction, Middle Cerebral Artery, Ischemic Attack, Transient, Mice, Mitogen-Activated Protein Kinases, N-Methylaspartate, Nerve Growth Factor, Nerve Growth Factors, Neurites, Neurons, Neuroprotective Agents, Oximes, PC12 Cells, Phosphorylation, Rats, Receptor, trkA, Signal Transduction",
author = "Lone Dag{\o} and Christian Bonde and Dan Peters and Arne M{\o}ller and Bomholt, {Signe Fars{\o}} and Hartz, {J Barbara P} and Morten Meyer and J{\o}rgen Drejer and Mette Gr{\o}nborg",
year = "2002",
month = "4",
day = "1",
language = "English",
volume = "81",
pages = "17--24",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
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Dagø, L, Bonde, C, Peters, D, Møller, A, Bomholt, SF, Hartz, JBP, Meyer, M, Drejer, J & Grønborg, M 2002, 'NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo.', Journal of Neurochemistry, bind 81, nr. 1, s. 17-24.

NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo. / Dagø, Lone; Bonde, Christian; Peters, Dan; Møller, Arne; Bomholt, Signe Farsø; Hartz, J Barbara P; Meyer, Morten; Drejer, Jørgen; Grønborg, Mette.

I: Journal of Neurochemistry, Bind 81, Nr. 1, 01.04.2002, s. 17-24.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo.

AU - Dagø, Lone

AU - Bonde, Christian

AU - Peters, Dan

AU - Møller, Arne

AU - Bomholt, Signe Farsø

AU - Hartz, J Barbara P

AU - Meyer, Morten

AU - Drejer, Jørgen

AU - Grønborg, Mette

PY - 2002/4/1

Y1 - 2002/4/1

N2 - NS 1231 [5-(4-chlorophenyl)-6,7,8,9-tetrahydro-1H-pyrrolo-[3.2-h]naphthalene-2,3-dione-3-oxime] belongs to a chemical series of compounds, which exhibit neurotrophic-like activities. In vitro, NS 1231 rescued nerve growth factor (NGF)-differentiated PC12 cells from death induced by withdrawal of trophic factors. In addition, NS 1231 stimulated NGF-induced neurite outgrowth of undifferentiated PC12 cells. At the molecular level, NS 1231 enhanced NGF-induced signalling events, such as TrkA phosphorylation at the Shc-binding site Tyr490 as well as ERK activation in PC12 cells. Moreover, NS 1231 reduced NMDA-induced excitotoxicity in organotypic hippocampal slice cultures. In a gerbil model of transient global ischaemia, treatment with NS 1231 reduced the delayed loss of neurons in the hippocampal CA1 layer. Furthermore, NS 1231 treatment resulted in a 43% reduction in total infarct volume in the mouse middle cerebral artery occlusion (MCAO) model. The present data thus implicate a therapeutic potential of NS 1231 or structural analogues in treatment of cerebral ischaemia.

AB - NS 1231 [5-(4-chlorophenyl)-6,7,8,9-tetrahydro-1H-pyrrolo-[3.2-h]naphthalene-2,3-dione-3-oxime] belongs to a chemical series of compounds, which exhibit neurotrophic-like activities. In vitro, NS 1231 rescued nerve growth factor (NGF)-differentiated PC12 cells from death induced by withdrawal of trophic factors. In addition, NS 1231 stimulated NGF-induced neurite outgrowth of undifferentiated PC12 cells. At the molecular level, NS 1231 enhanced NGF-induced signalling events, such as TrkA phosphorylation at the Shc-binding site Tyr490 as well as ERK activation in PC12 cells. Moreover, NS 1231 reduced NMDA-induced excitotoxicity in organotypic hippocampal slice cultures. In a gerbil model of transient global ischaemia, treatment with NS 1231 reduced the delayed loss of neurons in the hippocampal CA1 layer. Furthermore, NS 1231 treatment resulted in a 43% reduction in total infarct volume in the mouse middle cerebral artery occlusion (MCAO) model. The present data thus implicate a therapeutic potential of NS 1231 or structural analogues in treatment of cerebral ischaemia.

KW - Animals

KW - Cell Survival

KW - Disease Models, Animal

KW - Dose-Response Relationship, Drug

KW - Drug Evaluation, Preclinical

KW - Enzyme Activation

KW - Gerbillinae

KW - Hippocampus

KW - Indoles

KW - Infarction, Middle Cerebral Artery

KW - Ischemic Attack, Transient

KW - Mice

KW - Mitogen-Activated Protein Kinases

KW - N-Methylaspartate

KW - Nerve Growth Factor

KW - Nerve Growth Factors

KW - Neurites

KW - Neurons

KW - Neuroprotective Agents

KW - Oximes

KW - PC12 Cells

KW - Phosphorylation

KW - Rats

KW - Receptor, trkA

KW - Signal Transduction

M3 - Journal article

C2 - 12067229

VL - 81

SP - 17

EP - 24

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 1

ER -

Dagø L, Bonde C, Peters D, Møller A, Bomholt SF, Hartz JBP et al. NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo. Journal of Neurochemistry. 2002 apr 1;81(1):17-24.