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Neoechinulin A suppresses amyloid-β oligomer-induced microglia activation and thereby protects PC-12 cells from inflammation-mediated toxicity.
Neurotoxicology 2013; 35:30-40N

Abstract

A pathological hallmark of Alzheimer's disease (AD), aggregation and deposition of amyloid-β peptides, has been recognized as a potent activator of microglia-mediated neuroinflammation and neuronal dysfunction. Therefore, downregulation of microglial activation has a significant therapeutic demand. In this study, focus was given to evaluate the ability of neoechinulin A, an indole alkaloid isolated from marine-derived Microsporum sp., to attenuate microglial activation by oligomeric amyloid-β 1-42 (Aβ42). Neoechinulin A treatment significantly inhibited the generation of reactive oxygen and nitrogen species in Aβ42-activated BV-2 microglia cells. In addition, we found that neoechinulin A significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells. Moreover, the treatment downregulated the protein and gene expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β and IL-6. Further, activated microglia-mediated apoptosis of PC-12 pheochromocytoma cells was significantly repressed by neoechinulin A. The molecular mechanism studies suggested that neoechinulin A may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits. Regulation of these signalling pathways have most probably contributed to the anti-inflammatory activity of neoechinulin A. Collectively, these results suggest that with further studies neoechinulin A have a potential to be developed as a modulator of neuroinflammatory process in AD.

Authors+Show Affiliations

Marine Biochemistry Laboratory, Department of Chemistry, Pukyong National University, Busan 608-737, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23261590

Citation

Dewapriya, Pradeep, et al. "Neoechinulin a Suppresses Amyloid-β Oligomer-induced Microglia Activation and Thereby Protects PC-12 Cells From Inflammation-mediated Toxicity." Neurotoxicology, vol. 35, 2013, pp. 30-40.
Dewapriya P, Li YX, Himaya SW, et al. Neoechinulin A suppresses amyloid-β oligomer-induced microglia activation and thereby protects PC-12 cells from inflammation-mediated toxicity. Neurotoxicology. 2013;35:30-40.
Dewapriya, P., Li, Y. X., Himaya, S. W., Pangestuti, R., & Kim, S. K. (2013). Neoechinulin A suppresses amyloid-β oligomer-induced microglia activation and thereby protects PC-12 cells from inflammation-mediated toxicity. Neurotoxicology, 35, pp. 30-40. doi:10.1016/j.neuro.2012.12.004.
Dewapriya P, et al. Neoechinulin a Suppresses Amyloid-β Oligomer-induced Microglia Activation and Thereby Protects PC-12 Cells From Inflammation-mediated Toxicity. Neurotoxicology. 2013;35:30-40. PubMed PMID: 23261590.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neoechinulin A suppresses amyloid-β oligomer-induced microglia activation and thereby protects PC-12 cells from inflammation-mediated toxicity. AU - Dewapriya,Pradeep, AU - Li,Yong-Xin, AU - Himaya,S W A, AU - Pangestuti,Ratih, AU - Kim,Se-Kwon, Y1 - 2012/12/21/ PY - 2012/06/30/received PY - 2012/12/08/revised PY - 2012/12/14/accepted PY - 2012/12/25/entrez PY - 2012/12/25/pubmed PY - 2013/9/11/medline SP - 30 EP - 40 JF - Neurotoxicology JO - Neurotoxicology VL - 35 N2 - A pathological hallmark of Alzheimer's disease (AD), aggregation and deposition of amyloid-β peptides, has been recognized as a potent activator of microglia-mediated neuroinflammation and neuronal dysfunction. Therefore, downregulation of microglial activation has a significant therapeutic demand. In this study, focus was given to evaluate the ability of neoechinulin A, an indole alkaloid isolated from marine-derived Microsporum sp., to attenuate microglial activation by oligomeric amyloid-β 1-42 (Aβ42). Neoechinulin A treatment significantly inhibited the generation of reactive oxygen and nitrogen species in Aβ42-activated BV-2 microglia cells. In addition, we found that neoechinulin A significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells. Moreover, the treatment downregulated the protein and gene expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β and IL-6. Further, activated microglia-mediated apoptosis of PC-12 pheochromocytoma cells was significantly repressed by neoechinulin A. The molecular mechanism studies suggested that neoechinulin A may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits. Regulation of these signalling pathways have most probably contributed to the anti-inflammatory activity of neoechinulin A. Collectively, these results suggest that with further studies neoechinulin A have a potential to be developed as a modulator of neuroinflammatory process in AD. SN - 1872-9711 UR - https://www.unboundmedicine.com/medline/citation/23261590/Neoechinulin_A_suppresses_amyloid_β_oligomer_induced_microglia_activation_and_thereby_protects_PC_12_cells_from_inflammation_mediated_toxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(12)00305-1 DB - PRIME DP - Unbound Medicine ER -