Prevention of synaptic loss in cortico-hippocampal culture by silencing Kremen1 with siRNA

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Amanda Fisher (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Research has shown that Alzheimer's disease could be a result of an accumulation of amyloid ß (Aß) plaques and tau protein. The accumulation of Aß activates p53 , which leads to an increase of Dickkopf-1 (Dkk1). When Dkk1 is produced it binds to the protein Kremen1 which inhibits the LRP5/6 coreceptor disrupting the Wnt signaling pathway. This interruption leads to synaptic loss to the neurons in the brain causing behavioral deficits seen in Alzheimer's disease. This research shows small interfering RNA (siRNA) bounded to a rabies virus glycoprotein (RVG) can be delivered to the mouse brain. In addition we observed that siRNAs can downregulate Kremen1; stopping the synaptic loss in neurons along with an increase in axon length in cortico-hippocampal culture at both 72 and 96 hour transfection.

Additional Information

Publication

Thesis

Language: English

Date: 2017

Keywords

Alzheimer's Disease, cortico-hippocampal culture, Kremen1, Dickkopf-1 (Dkk1)

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