title: Hexa (ethylene glycol) derivative of benzothiazole aniline promotes dendritic spine formation through the RasGRF1-Ras dependent pathway.
abstract: Our recent study demonstrated that an amyloid-β binding molecule, BTA-EG4, increases dendritic spine number via Ras-mediated signaling. To potentially optimize the potency of the BTA compounds, we synthesized and evaluated an amyloid-β binding analog of BTA-EG4 with increased solubility in aqueous solution, BTA-EG6. We initially examined the effects of BTA-EG6 on dendritic spine formation and found that BTA-EG6-treated primary hippocampal neurons had significantly increased dendritic spine number compared to control treatment. In addition, BTA-EG6 significantly increased the surface level of AMPA receptors. Upon investigation into the molecular mechanism by which BTA-EG6 promotes dendritic spine formation, we found that BTA-EG6 may exert its effects on spinogenesis via RasGRF1-ERK signaling, with potential involvement of other spinogenesis-related proteins such as Cdc42 and CDK5. Taken together, our data suggest that BTA-EG6 boosts spine and synapse number, which may have a beneficial effect of enhancing neuronal and synaptic function in the normal healthy brain.
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Nathanael J
authors.initials: NJ
authors.lastname: Lee
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Song
authors.affiliation: Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: You Me
authors.initials: YM
authors.lastname: Sung
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Taehee
authors.initials: T
authors.lastname: Lee
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chung
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Sung-Ha
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Cifelli
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Rubinshtein
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Lila K
authors.initials: LK
authors.lastname: Habib
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Christina C
authors.initials: CC
authors.lastname: Capule
authors.affiliation: Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Turner
authors.affiliation: Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Daniel T S
authors.initials: DT
authors.lastname: Pak
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea. Electronic address: sookhoe72@kbri.re.kr.
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Hoe
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles / Q000737:chemistry* / Q000494:pharmacology*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D019855:Ethylene Glycol / Q000737:chemistry / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018631:ras Proteins / Q000378:metabolism*; D020666:ras-GRF1 / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D052160:Benzothiazoles; D018091:Receptors, AMPA; D020666:ras-GRF1; D018631:ras Proteins; D019855:Ethylene Glycol
keywords: BTA-EG6; Dendritic spine; Rap signaling; Ras signaling