Chemicals possessing a neurotrophin-like activity on dopaminergic neurons in primary culture.
BACKGROUND:Neurotrophic factors have been shown to possess strong neuroprotective and neurorestaurative properties in Parkinson's disease patients. However the issues to control their delivery into the interest areas of the brain and their surgical administration linked to their unability to cr...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2009-07-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC2704893?pdf=render |
id |
doaj-9db6224a99b24f1fb57f6a3911add00c |
---|---|
record_format |
Article |
spelling |
doaj-9db6224a99b24f1fb57f6a3911add00c2020-11-25T00:42:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-07-0147e621510.1371/journal.pone.0006215Chemicals possessing a neurotrophin-like activity on dopaminergic neurons in primary culture.Fanny SchmidtPierre ChampyBlandine Séon-MénielXavier FranckRita Raisman-VozariBruno FigadèreBACKGROUND:Neurotrophic factors have been shown to possess strong neuroprotective and neurorestaurative properties in Parkinson's disease patients. However the issues to control their delivery into the interest areas of the brain and their surgical administration linked to their unability to cross the blood brain barrier are many drawbacks responsible of undesirable side effects limiting their clinical use. A strategy implying the use of neurotrophic small molecules could provide an interesting alternative avoiding neurotrophin administration and side effects. In an attempt to develop drugs mimicking neurotrophic factors, we have designed and synthesized low molecular weight molecules that exhibit neuroprotective and neuritogenic potential for dopaminergic neurons. PRINCIPAL FINDINGS:A cell-based screening of an in-house quinoline-derived compound collection led to the characterization of compounds exhibiting both activities in the nanomolar range on mesencephalic dopaminergic neurons in spontaneous or 1-methyl-4-phenylpyridinium (MPP(+))-induced neurodegeneration. This study provides evidence that rescued neurons possess a functional dopamine transporter and underlines the involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in these processes. CONCLUSION:Cell-based screening led to the discovery of a potent neurotrophic compound possessing expected physico-chemical properties for blood brain barrier penetration as a serious candidate for therapeutic use in Parkinson disease.http://europepmc.org/articles/PMC2704893?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fanny Schmidt Pierre Champy Blandine Séon-Méniel Xavier Franck Rita Raisman-Vozari Bruno Figadère |
spellingShingle |
Fanny Schmidt Pierre Champy Blandine Séon-Méniel Xavier Franck Rita Raisman-Vozari Bruno Figadère Chemicals possessing a neurotrophin-like activity on dopaminergic neurons in primary culture. PLoS ONE |
author_facet |
Fanny Schmidt Pierre Champy Blandine Séon-Méniel Xavier Franck Rita Raisman-Vozari Bruno Figadère |
author_sort |
Fanny Schmidt |
title |
Chemicals possessing a neurotrophin-like activity on dopaminergic neurons in primary culture. |
title_short |
Chemicals possessing a neurotrophin-like activity on dopaminergic neurons in primary culture. |
title_full |
Chemicals possessing a neurotrophin-like activity on dopaminergic neurons in primary culture. |
title_fullStr |
Chemicals possessing a neurotrophin-like activity on dopaminergic neurons in primary culture. |
title_full_unstemmed |
Chemicals possessing a neurotrophin-like activity on dopaminergic neurons in primary culture. |
title_sort |
chemicals possessing a neurotrophin-like activity on dopaminergic neurons in primary culture. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2009-07-01 |
description |
BACKGROUND:Neurotrophic factors have been shown to possess strong neuroprotective and neurorestaurative properties in Parkinson's disease patients. However the issues to control their delivery into the interest areas of the brain and their surgical administration linked to their unability to cross the blood brain barrier are many drawbacks responsible of undesirable side effects limiting their clinical use. A strategy implying the use of neurotrophic small molecules could provide an interesting alternative avoiding neurotrophin administration and side effects. In an attempt to develop drugs mimicking neurotrophic factors, we have designed and synthesized low molecular weight molecules that exhibit neuroprotective and neuritogenic potential for dopaminergic neurons. PRINCIPAL FINDINGS:A cell-based screening of an in-house quinoline-derived compound collection led to the characterization of compounds exhibiting both activities in the nanomolar range on mesencephalic dopaminergic neurons in spontaneous or 1-methyl-4-phenylpyridinium (MPP(+))-induced neurodegeneration. This study provides evidence that rescued neurons possess a functional dopamine transporter and underlines the involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in these processes. CONCLUSION:Cell-based screening led to the discovery of a potent neurotrophic compound possessing expected physico-chemical properties for blood brain barrier penetration as a serious candidate for therapeutic use in Parkinson disease. |
url |
http://europepmc.org/articles/PMC2704893?pdf=render |
work_keys_str_mv |
AT fannyschmidt chemicalspossessinganeurotrophinlikeactivityondopaminergicneuronsinprimaryculture AT pierrechampy chemicalspossessinganeurotrophinlikeactivityondopaminergicneuronsinprimaryculture AT blandineseonmeniel chemicalspossessinganeurotrophinlikeactivityondopaminergicneuronsinprimaryculture AT xavierfranck chemicalspossessinganeurotrophinlikeactivityondopaminergicneuronsinprimaryculture AT ritaraismanvozari chemicalspossessinganeurotrophinlikeactivityondopaminergicneuronsinprimaryculture AT brunofigadere chemicalspossessinganeurotrophinlikeactivityondopaminergicneuronsinprimaryculture |
_version_ |
1725280875210342400 |