PUBLICATION
Neuroprotective Effect of the Marine-Derived Compound 11-Dehydrosinulariolide through DJ-1-Related Pathway in In Vitro and In Vivo Models of Parkinson's Disease
- Authors
- Feng, C.W., Hung, H.C., Huang, S.Y., Chen, C.H., Chen, Y.R., Chen, C.Y., Yang, S.N., Wang, H.D., Sung, P.J., Sheu, J.H., Tsui, K.H., Chen, W.F., Wen, Z.H.
- ID
- ZDB-PUB-161025-25
- Date
- 2016
- Source
- Marine drugs 14(10): (Journal)
- Registered Authors
- Keywords
- CREB, DJ-1, HO-1, Parkinson’s disease, neuroprotection, zebrafish
- MeSH Terms
-
- Animals
- Antiparkinson Agents/pharmacology*
- Cell Line
- Diterpenes/pharmacology*
- Gene Knockdown Techniques
- Humans
- Hydroxydopamines
- Male
- Mitochondria/chemistry
- Neuroprotective Agents/pharmacology*
- Parkinson Disease/drug therapy*
- Parkinson Disease, Secondary/chemically induced
- Parkinson Disease, Secondary/drug therapy
- Protein Deglycase DJ-1/biosynthesis
- Protein Deglycase DJ-1/drug effects*
- Protein Deglycase DJ-1/genetics
- RNA, Small Interfering/pharmacology
- Rats
- Rats, Wistar
- Signal Transduction/drug effects
- Swimming
- Tyrosine 3-Monooxygenase/metabolism
- Zebrafish
- PubMed
- 27763504 Full text @ Mar. Drugs
Citation
Feng, C.W., Hung, H.C., Huang, S.Y., Chen, C.H., Chen, Y.R., Chen, C.Y., Yang, S.N., Wang, H.D., Sung, P.J., Sheu, J.H., Tsui, K.H., Chen, W.F., Wen, Z.H. (2016) Neuroprotective Effect of the Marine-Derived Compound 11-Dehydrosinulariolide through DJ-1-Related Pathway in In Vitro and In Vivo Models of Parkinson's Disease. Marine drugs. 14(10).
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de) upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA)-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways. Additionally, we found that 11-de could reverse the 6-OHDA-induced downregulation of total swimming distance in a zebrafish model of PD. Using a rat model of PD, we showed that a 6-OHDA-induced increase in the number of turns, and increased time spent by rats on the beam, could be reversed by 11-de treatment. Lastly, we showed that 6-OHDA-induced attenuation in tyrosine hydroxylase (TH), a dopaminergic neuronal marker, in zebrafish and rat models of PD could also be reversed by treatment with 11-de. Moreover, the patterns of DJ-1 expression observed in this study in the zebrafish and rat models of PD corroborated the trend noted in previous in vitro studies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping