This is Your Mouse on Celastrol The Behavioral Effects of Celastrol on a Transgenic Mouse Model of Alzheimer's Disease

Amelia March

Date of Award

2010

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Beulig, Alfred

Keywords

Alzheimer's Disease, Mouse, Celastrol

Area of Concentration

Biology

Abstract

The NFκB inhibiting compound Celastrol has been shown to lower levels of Aβ, an amino acidpeptide known to be a major component of the senile plaques seen in the brains of individuals with Alzheimer�s disease, both in vivo and in vitro. Celastrol has also been found to reduce the production of βCTF and β-sAPP, which both result from cleavage of the APP ectodomain by the protease �secretase (BACE-1) at the N-terminus of Aβ. Thus, one likely method by which Celastrol lowers brain Aβ burden is by decreasing the expression of BACE-1, in turn reducing the expression of the substrate βCTF, which results in Aβ production after proteolytic processing by γ secretase. The memory and ability-based performance of two strains of mice (Tg APPsw and Tg PS1/ APPsw) administered Celastrol or a placebo were tested by the Morris Water Maze, Y-maze, and Rota Rod tests. The Tg APPsw strain overexpresses both human Aβ (1-42) and Aβ (1-40), and the Tg PS1/APPsw strain has an i crease in the Aβ (1-42) to Aβ (1-40) ratio. Brain Aβ levels of these mice were also quantified after a long term and an acute study. These studies revealed that Celastrol is likely to be most useful as a prophylactic treatment rather than a therapeutic one.

Rights

This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.

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