Dr. Satoh studies PEDs: Pro-Electrophilic Drugs as Drug Candidates for the Brain
Dr. Satoh received his Ph.D. from Kyoto University, Japan.
Dual neuroprotective pathways of a pro-electrophilic compound via HSF-1-activated heat-shock proteins and Nrf2-activated phase 2 antioxidant response enzymes.
Satoh T, Rezaie T, Seki M, Sunico CR, Tabuchi T, Kitagawa T, Yanagitai M, Senzaki M, Kosegawa C, Taira H, McKercher SR, Hoffman JK, Roth GP, Lipton SA
J Neurochem. 2011 Nov;119(3):569-78
Carnosic acid and carnosol inhibit adipocyte differentiation in mouse 3T3-L1 cells through induction of phase2 enzymes and activation of glutathione metabolism.
Takahashi T, Tabuchi T, Tamaki Y, Kosaka K, Takikawa Y, Satoh T
Biochem Biophys Res Commun. 2009 May 8;382(3):549-54
Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1.
Satoh T, Kosaka K, Itoh K, Kobayashi A, Yamamoto M, Shimojo Y, Kitajima C, Cui J, Kamins J, Okamoto S, Izumi M, Shirasawa T, Lipton SA
J Neurochem. 2008 Feb;104(4):1116-31
Redox regulation of neuronal survival mediated by electrophilic compounds.
Satoh T, Lipton SA
Trends Neurosci. 2007 Jan;30(1):37-45
Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophilic [correction of electrophillic] phase II inducers.
Satoh T, Okamoto SI, Cui J, Watanabe Y, Furuta K, Suzuki M, Tohyama K, Lipton SA
Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):768-73
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Characterization of an α-glucosidase, HdAgl, from the digestive fluid of Haliotis discus hannai.
Satoh T, Inoue A, Ojima T
Comp Biochem Physiol B Biochem Mol Biol. 2013 Jun 14;
Rhodium(III)-catalyzed Oxidative Coupling through C-H Bond Cleavage Directed by Phosphinoxy Groups.
Unoh Y, Hashimoto Y, Takeda D, Hirano K, Satoh T, Miura M
Org Lett. 2013 Jun 17;
Pulmonary Edema Predictive Scoring Index (PEPSI), a New Index to Predict Risk of Reperfusion Pulmonary Edema and Improvement of Hemodynamics in Percutaneous Transluminal Pulmonary Angioplasty.
Inami T, Kataoka M, Shimura N, Ishiguro H, Yanagisawa R, Taguchi H, Fukuda K, Yoshino H, Satoh T
JACC Cardiovasc Interv. 2013 Jun 7;
Takumi Satoh's Research Focus
Alzheimer's Disease, Neurodegenerative and Neuromuscular Diseases, Aging-Related Diseases
Dr. Satoh has studied the technology based on the discovery of naturally-occuring molecules with activity against oxidative/ER stress-related injury in the CNS by activating the Keap1/Nrf2 and HSP90/HSF-1 pathways. His study targets Age-related Macular Degeneration and secondly targets Alzheimer's disease.
Takumi Satoh's Research Report
A novel aspect of the proposal is that the compounds will be "pro-electrophilic" and converted to become "electrophilic"
through auto-oxidation. These pro-electrophilic compounds should manifest protective effects on eyes and brain with very few
side effects. Importantly, these compounds are not themselves electrophilic until they become electrophilic through auto-oxidation.
Because of these pro-electophilic properties, we termed these agents Pro-Electrophilic Drugs (PEDs).
Redox stress is thought to contribute to neurodegenerative disorders, including Alzheimer's and Parkinsons's diseases. With prolonged
oxidative stress, cells mount a 'counterattack' to activate transcription-dependent pathways, including the Keap1/Nrf2 and HSP90/HSF-1
pathways, which induce phase 2 enzymes and heat-shock proteins, respectively. PEDs have been shown to signal an "electrophilic counterattack,"
binding to specific cysteines of Keap1 and HSP90 to activate these pathways.
Further, we studied novel pro-electrophilic drugs (PEDs) that are activated by the very oxidative/nitrosative stress that they
subsequently counteract. One example is carnosic acid (CA), found in the herb rosemary. CA itself is not electrophilic, but in response to
oxidation becomes electrophilic, and then activates the Keap1/Nrf2 pathway. PEDs appear to have minimal side effects, in part because they are
generated preferentially in cells experienceing oxidative stress.