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Conference Paper: N-Propargyl caffeamide (PACA) ameliorates MPTP-induced dopaminergic neurodegeneration and motor impairments via activating Keap1-Nrf2 pathway and inducing NGF expression
Title | N-Propargyl caffeamide (PACA) ameliorates MPTP-induced dopaminergic neurodegeneration and motor impairments via activating Keap1-Nrf2 pathway and inducing NGF expression |
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Authors | |
Issue Date | 2016 |
Citation | The 15th Meeting of the Consortium for Globalization of Chinese Medicine (CGCM 2016), Academia Sinica, Taipei, Taiwan, 23-25 August 2016. How to Cite? |
Abstract | Insufficient production of neurotrophic factors is implicated in various neurodegenerative disorders. We recently synthesized a novel caffeic acid derivative N-propargyl caffeamide (PACA) and discovered the neuroprotective and neuritogenic activities of PACA in cell culture system (Yang CB et al ACS Chem Neurosci 2015 Sep 16;6(9):1560-9). The aim of the present study was to evaluate the potential of PACA in the treatment of MPTP-induced dopaminergic neurodegeneration and motor impairments and the underlying mechanism. was discovered that PACA not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine (6-OHDA) neurotoxicity in dopaminergic PC12 cells and primary rat midbrain neurons. To identify the PACA-binding proteins, a biotin tag was introduced to the covalent PACA-protein adducts via “Click chemistry” alkyne-azido cycloaddition. As a result, kelch-like ECH-associated protein 1 (Keap1) was isolated as the predominant protein from PACA treated PC12 cells. It was demonstrated that the formation of PACA-Keap1 conjugates induced the nuclear translocation of transcription factor Nrf2 and the expression of antioxidant heme oxygenase-1 (HO-1). Importantly, specific HO-1 inhibitor SnPP diminished the neuroprotective and neuritogenic activities of PACA. Moreover, PACA attenuated 6-OHDA-induced production of neurotoxic reactive oxygen species and reactive nitrogen species. PACA also preserved mitochondrial membrane integrity and enhanced the cellular resistance against 6-OHDA neurotoxicity. These results suggest that PACA exhibits neuroprotective and neuritogenic activities via activating the Nrf2/HO-1 antioxidant pathway. |
Persistent Identifier | http://hdl.handle.net/10722/233086 |
DC Field | Value | Language |
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dc.contributor.author | Luo, D | - |
dc.contributor.author | Zhao, J | - |
dc.contributor.author | Cheng, Y | - |
dc.contributor.author | Lee, S | - |
dc.contributor.author | Rong, J | - |
dc.date.accessioned | 2016-09-20T05:34:26Z | - |
dc.date.available | 2016-09-20T05:34:26Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | The 15th Meeting of the Consortium for Globalization of Chinese Medicine (CGCM 2016), Academia Sinica, Taipei, Taiwan, 23-25 August 2016. | - |
dc.identifier.uri | http://hdl.handle.net/10722/233086 | - |
dc.description.abstract | Insufficient production of neurotrophic factors is implicated in various neurodegenerative disorders. We recently synthesized a novel caffeic acid derivative N-propargyl caffeamide (PACA) and discovered the neuroprotective and neuritogenic activities of PACA in cell culture system (Yang CB et al ACS Chem Neurosci 2015 Sep 16;6(9):1560-9). The aim of the present study was to evaluate the potential of PACA in the treatment of MPTP-induced dopaminergic neurodegeneration and motor impairments and the underlying mechanism. was discovered that PACA not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine (6-OHDA) neurotoxicity in dopaminergic PC12 cells and primary rat midbrain neurons. To identify the PACA-binding proteins, a biotin tag was introduced to the covalent PACA-protein adducts via “Click chemistry” alkyne-azido cycloaddition. As a result, kelch-like ECH-associated protein 1 (Keap1) was isolated as the predominant protein from PACA treated PC12 cells. It was demonstrated that the formation of PACA-Keap1 conjugates induced the nuclear translocation of transcription factor Nrf2 and the expression of antioxidant heme oxygenase-1 (HO-1). Importantly, specific HO-1 inhibitor SnPP diminished the neuroprotective and neuritogenic activities of PACA. Moreover, PACA attenuated 6-OHDA-induced production of neurotoxic reactive oxygen species and reactive nitrogen species. PACA also preserved mitochondrial membrane integrity and enhanced the cellular resistance against 6-OHDA neurotoxicity. These results suggest that PACA exhibits neuroprotective and neuritogenic activities via activating the Nrf2/HO-1 antioxidant pathway. | - |
dc.language | eng | - |
dc.relation.ispartof | Meeting of Consortium for Globalization of Chinese Medicine, CGCM 2016 | - |
dc.relation.ispartof | 第15屆中藥全球化聯盟會議 | - |
dc.title | N-Propargyl caffeamide (PACA) ameliorates MPTP-induced dopaminergic neurodegeneration and motor impairments via activating Keap1-Nrf2 pathway and inducing NGF expression | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Zhao, J: zhaojia7@hku.hk | - |
dc.identifier.email | Rong, J: jrong@hku.hk | - |
dc.identifier.authority | Rong, J=rp00515 | - |
dc.identifier.hkuros | 264421 | - |