File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Discovery of a novel neuroprotectant, BHDPC, that protects against MPP+/MPTP-induced neuronal death in multiple experimental models

TitleDiscovery of a novel neuroprotectant, BHDPC, that protects against MPP<sup>+</sup>/MPTP-induced neuronal death in multiple experimental models
Authors
KeywordsMPP +
Neurodegeneration
Rat organotypiccerebellarcultures
Zebrafish
Issue Date2015
Citation
Free Radical Biology and Medicine, 2015, v. 89, p. 1057-1066 How to Cite?
AbstractProgressive degeneration and death of neurons are main causes of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Although some current medicines may temporarily improve their symptoms, no treatments can slow or halt the progression of neuronal death. In this study, a pyrimidine derivative, benzyl 7-(4-hydroxy-3-methoxyphenyl)-5-methyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate (BHDPC), was found to attenuate dramatically the MPTP-induced death of dopaminergic neurons and improve behavior movement deficiency in zebrafish, supporting its potential neuroprotective activity in vivo. Further study in rat organotypic cerebellar cultures indicated that BHDPC was able to suppress MPP+-induced cell death of brain tissue slices ex vivo. The protective effect of BHDPC against MPP+ toxicity was also effective in human neuroblastoma SH-SY5Y cells through restoring abnormal changes in mitochondrial membrane potential and numerous apoptotic regulators. Western blotting analysis indicated that BHDPC was able to activate PKA/CREB survival signaling and further up-regulate Bcl2 expression. However, BHDPC failed to suppress MPP+-induced cytotoxicity and the increase of caspase 3 activity in the presence of the PKA inhibitor H89. Taken together, these results suggest that BHDPC is a potential neuroprotectant with prosurvival effects in multiple models of neurodegenerative disease in vitro, ex vivo, and in vivo.
Persistent Identifierhttp://hdl.handle.net/10722/335785
ISSN
2023 Impact Factor: 7.1
2023 SCImago Journal Rankings: 1.752
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChong, Cheong Meng-
dc.contributor.authorMa, Dan-
dc.contributor.authorZhao, Chao-
dc.contributor.authorFranklin, Robin J.M.-
dc.contributor.authorZhou, Zhong Yan-
dc.contributor.authorAi, Nana-
dc.contributor.authorLi, Chuwen-
dc.contributor.authorYu, Huidong-
dc.contributor.authorHou, Tingjun-
dc.contributor.authorSa, Fei-
dc.contributor.authorMing-Yuen Lee, Simon-
dc.date.accessioned2023-12-28T08:48:44Z-
dc.date.available2023-12-28T08:48:44Z-
dc.date.issued2015-
dc.identifier.citationFree Radical Biology and Medicine, 2015, v. 89, p. 1057-1066-
dc.identifier.issn0891-5849-
dc.identifier.urihttp://hdl.handle.net/10722/335785-
dc.description.abstractProgressive degeneration and death of neurons are main causes of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Although some current medicines may temporarily improve their symptoms, no treatments can slow or halt the progression of neuronal death. In this study, a pyrimidine derivative, benzyl 7-(4-hydroxy-3-methoxyphenyl)-5-methyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate (BHDPC), was found to attenuate dramatically the MPTP-induced death of dopaminergic neurons and improve behavior movement deficiency in zebrafish, supporting its potential neuroprotective activity in vivo. Further study in rat organotypic cerebellar cultures indicated that BHDPC was able to suppress MPP+-induced cell death of brain tissue slices ex vivo. The protective effect of BHDPC against MPP+ toxicity was also effective in human neuroblastoma SH-SY5Y cells through restoring abnormal changes in mitochondrial membrane potential and numerous apoptotic regulators. Western blotting analysis indicated that BHDPC was able to activate PKA/CREB survival signaling and further up-regulate Bcl2 expression. However, BHDPC failed to suppress MPP+-induced cytotoxicity and the increase of caspase 3 activity in the presence of the PKA inhibitor H89. Taken together, these results suggest that BHDPC is a potential neuroprotectant with prosurvival effects in multiple models of neurodegenerative disease in vitro, ex vivo, and in vivo.-
dc.languageeng-
dc.relation.ispartofFree Radical Biology and Medicine-
dc.subjectMPP +-
dc.subjectNeurodegeneration-
dc.subjectRat organotypiccerebellarcultures-
dc.subjectZebrafish-
dc.titleDiscovery of a novel neuroprotectant, BHDPC, that protects against MPP<sup>+</sup>/MPTP-induced neuronal death in multiple experimental models-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.freeradbiomed.2015.08.013-
dc.identifier.pmid26415025-
dc.identifier.scopuseid_2-s2.0-84946560842-
dc.identifier.volume89-
dc.identifier.spage1057-
dc.identifier.epage1066-
dc.identifier.eissn1873-4596-
dc.identifier.isiWOS:000366355800099-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats