title: 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.
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.
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung 804, Taiwan. qscjuejuejue@gmail.com.|Doctoral Degree Program in Marine Biotechnology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan. qscjuejuejue@gmail.com.|Marine Biomedical Laboratory & Center for Translational Biopharmaceuticals, Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan. qscjuejuejue@gmail.com.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Feng
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung 804, Taiwan. hanchun25@gmail.com.|Doctoral Degree Program in Marine Biotechnology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan. hanchun25@gmail.com.|Marine Biomedical Laboratory & Center for Translational Biopharmaceuticals, Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan. hanchun25@gmail.com.
authors.forename: Han-Chun
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Marine Biomedical Laboratory & Center for Translational Biopharmaceuticals, Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan. johnjohnkings@gmail.com.|College of Oceanology and Food Science, Quanzhou Normal University, Quanzhou 362000, China. johnjohnkings@gmail.com.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung 804, Taiwan. anubis0620@gmail.com.|Doctoral Degree Program in Marine Biotechnology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan. anubis0620@gmail.com.|Marine Biomedical Laboratory & Center for Translational Biopharmaceuticals, Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan. anubis0620@gmail.com.
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan. yrchen@gate.sinica.edu.tw.
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan. biogoldfish@mail2000.com.tw.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, E-DA Hospital, School of Medicine, College of Medicine, I-SHOU University, Kaohsiung 840, Taiwan. y520729@gmail.com.
authors.forename: San-Nan
authors.initials: SN
authors.lastname: Yang
authors.affiliation: College of Oceanology and Food Science, Quanzhou Normal University, Quanzhou 362000, China. davidw@dragon.nchu.edu.tw.|Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung 402, Taiwan. davidw@dragon.nchu.edu.tw.|Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan. davidw@dragon.nchu.edu.tw.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan. davidw@dragon.nchu.edu.tw.
authors.forename: Hui-Min David
authors.initials: HD
authors.lastname: Wang
authors.affiliation: Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan. pjsung@nmmba.gov.tw.|Taiwan Coral Research Center, National Museum of Marine Biology & Aquarium, Pingtung 944, Taiwan. pjsung@nmmba.gov.tw.
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung 804, Taiwan. sheu@mail.nsysu.edu.tw.|Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung 804, Taiwan. sheu@mail.nsysu.edu.tw.
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Sheu
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan. khtsui60@gmail.com.|Department of Obstetrics and Gynecology and Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan. khtsui60@gmail.com.|Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung County 907, Taiwan. khtsui60@gmail.com.
authors.forename: Kuan-Hao
authors.initials: KH
authors.lastname: Tsui
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung 804, Taiwan. ma4949@adm.cgmh.org.tw.|Department of Neurosurgery and Center for Parkinson Disease, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. ma4949@adm.cgmh.org.tw.
authors.forename: Wu-Fu
authors.initials: WF
authors.lastname: Chen
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung 804, Taiwan. wzh@mail.nsysu.edu.tw.|Marine Biomedical Laboratory & Center for Translational Biopharmaceuticals, Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan. wzh@mail.nsysu.edu.tw.|Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung 804, Taiwan. wzh@mail.nsysu.edu.tw.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002460:Cell Line; D004224:Diterpenes / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006801:Humans; D006892:Hydroxydopamines; D008297:Male; D008928:Mitochondria / Q000737:chemistry; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy; D000071617:Protein Deglycase DJ-1 / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013550:Swimming; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015027:Zebrafish
chemical_list: C569844:11-dehydrosinulariolide; D000978:Antiparkinson Agents; D004224:Diterpenes; D006892:Hydroxydopamines; D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; D014446:Tyrosine 3-Monooxygenase; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1
keywords: CREB; DJ-1; HO-1; Parkinson’s disease; neuroprotection; zebrafish