Therapeutic modulation of apoptosis: targeting the BCL-2 family at the interface of the mitochondrial membrane.

Yonsei Med J

Biomolecular Science Center, Burnett School of Biomedical Sciences, University of Central Florida, 12722 Research Parkway, Orlando, FL 32826, USA.

Published: October 2008

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615374PMC
http://dx.doi.org/10.3349/ymj.2008.49.5.689DOI Listing

Publication Analysis

Top Keywords

bcl-2 family
8
mitochondrial membrane
8
human disease
8
bcl-2 proteins
8
apoptosis
6
bcl-2
5
therapeutic modulation
4
modulation apoptosis
4
apoptosis targeting
4
targeting bcl-2
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!