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Publication : A tetra(ethylene glycol) derivative of benzothiazole aniline enhances Ras-mediated spinogenesis.

First Author  Megill A Year  2013
Journal  J Neurosci Volume  33
Issue  22 Pages  9306-18
PubMed ID  23719799 Mgi Jnum  J:198662
Mgi Id  MGI:5498614 Doi  10.1523/JNEUROSCI.1615-12.2013
Citation  Megill A, et al. (2013) A tetra(ethylene glycol) derivative of benzothiazole aniline enhances Ras-mediated spinogenesis. J Neurosci 33(22):9306-18
abstractText  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 Abeta-induced toxicity. However, the effects of Abeta-targeting molecules on other cellular processes, including those that modulate synaptic plasticity, remain unknown. We report here that BTA-EG4 decreases Abeta 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.
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