Author Type

Graduate Student

Date of Award

2012

Document Type

Thesis

Publication Status

Version of Record

Submission Date

October 2026

Abstract

Huntington's Disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine repeat within the Huntingtin gene IT15. In this study we demonstrated that Bcl-2 interacting mediator of cell death Extra Long (BimEL) protein expression was significantly increased in cells expressing mutant Huntingtin (mHtt). Moreover, striatal BimEL expression remained high in an R6/2 HD mouse model throughout the disease progression. Utilizing novel BimEL phospho-mutants we demonstrated the phosphorylation of Ser65 to be important for the stabilization of BimEL. We provided evidence that impaired proteasome function, increased JNK activity and reduced striatal BDNF lead to changes in the phosphorylation of BimEL, thereby promoting its stabilization specifically within the striatum of R6/2 mice. Furthermore, knocking down BimEL expression prevented mHtt-induced cell death in a HD cell culture. Taken together, these findings suggest that BimEL may contribute to the selective neurodegeneration and pathogenesis of HD.

Extent

ix, 101 p. : ill. (some col.)

Comments

by Rebecca Leon.|Thesis (Ph.D.)--Florida Atlantic University, 2012.|Includes bibliography.|Mode of access: World Wide Web.|System requirements: Adobe Reader.|by Rebecca Leon.

Identifier

FADT3355556

Format

pdf

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