Format

Send to

Choose Destination
Biochim Biophys Acta. 2016 Feb;1862(2):284-95. doi: 10.1016/j.bbadis.2015.12.007. Epub 2015 Dec 8.

Hexa (ethylene glycol) derivative of benzothiazole aniline promotes dendritic spine formation through the RasGRF1-Ras dependent pathway.

Author information

1
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
2
Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea.
3
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA.
4
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
5
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
6
Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA.
7
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20057, USA.
8
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.

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.

KEYWORDS:

BTA-EG6; Dendritic spine; Rap signaling; Ras signaling

PMID:
26675527
DOI:
10.1016/j.bbadis.2015.12.007
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center