A tetra(Ethylene Glycol) derivative of benzothiazole aniline enhances ras-mediated spinogenesis

Andrea Megill, Taehee Lee, Amanda Marie DiBattista, Jung Min Song, Matthew H. Spitzer, Mark Rubinshtein, Lila K. Habib, Christina C. Capule, Michael Mayer, R. Scott Turner, Alfredo Kirkwood, Jerry Yang, Daniel T.S. Pak, Hey Kyoung Lee, Hyang Sook Hoe

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The tetra(ethylene glycol) derivative of benzothiazole aniline, BTA-EG4, is a novel amyloid-binding small molecule that can penetrate the blood- brain barrier and protect cells from Aβ-induced toxicity. However, the effects of Aβ-targeting molecules on other cellular processes, including those that modulate synaptic plasticity, remain unknown. We report here that BTA-EG4 decreases Aβ levels, alters cell surface expression of amyloid precursor protein (APP), and improves memory in wild-type mice. Interestingly, the BTA-EG4-mediated behavioral improvement is not correlated with LTP, but with increased spinogenesis. The higher dendritic spine density reflects an increase in the number of functional synapses as determined by increased miniature EPSC (mEPSC) frequency without changes in presynaptic parameters or postsynaptic mEPSC amplitude. Additionally, BTA-EG4 requires APP to regulate dendritic spine density through a Ras signaling-dependent mechanism. Thus, BTA-EG4 may provide broad therapeutic benefits for improving neuronal and cognitive function, and may have implications in neurodegenerative disease therapy.

Original languageEnglish (US)
Pages (from-to)9306-9318
Number of pages13
JournalJournal of Neuroscience
Volume33
Issue number22
DOIs
StatePublished - May 29 2013

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