Title

Therapeutic Modulation of Apoptosis: Targeting the BCL-2 Family at the Interface of the Mitochondrial Membrane

Authors

Authors

K. N. Nemec;A. K. Khaled

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

Yonsei Med. J.

Keywords

Apoptosis; BAX; BH3; drug design; peptide therapy; PROGRAMMED CELL-DEATH; CYTOCHROME-C RELEASE; BAX TRANSLOCATION; MEMBER; BIM; FACTOR WITHDRAWAL; DEFICIENT MICE; PROTEIN; GENE; EXPRESSION; ELEGANS; Medicine, General & Internal

Abstract

A vast portion of human disease results when the process of apoptosis is defective. Disorders resulting from inappropriate cell death range from autoimmune and neurodegenerative conditions to heart disease. Conversely, prevention of apoptosis is the hallmark of cancer and confounds the efficacy of cancer therapeutics. In the search for optimal targets that would enable the control of apoptosis, members of the BCL-2 family of anti- and pro-apoptotic factors have figured prominently. Development of BCL-2 antisense approaches, small molecules, and BH3 peptidomimetics has met with both success and failure. Success-because BCL-2 proteins play essential roles in apoptosis. Failure-because single targets for drug development have limited scope. By examining the activity of the BCL-2 proteins in relation to the mitochondrial landscape and drawing attention to the significant mitochondrial membrane alterations that ensue during apoptosis, we demonstrate the need for a broader based multi-disciplinary approach for the design of novel apoptosis-modulating compounds in the treatment of human disease.

Journal Title

Yonsei Medical Journal

Volume

49

Issue/Number

5

Publication Date

1-1-2008

Document Type

Review

Language

English

First Page

689

Last Page

697

WOS Identifier

WOS:000260647300001

ISSN

0513-5796

Share

COinS