Modulating Mitochondria-Mediated Apoptotic Cell Death through Targeting of Bcl-2 Family Proteins
Abstract:Research demonstrated that the function of mitochondria extends well beyond that of being cell powerhouses and revealed that these organelles fulfil a dual role in both cellular life and death. In most vertebrates, execution of the mitochondrial pathway of apoptosis requires permeabilization of the mitochondrial outer membrane, an event which allows for the release of a variety of intramembrane space proteins, leading to the activation of caspases and ultimately cell demise. Bcl-2 family proteins, which include pro- and antiapoptotic members, positively or negatively regulate mitochondrial outer membrane permeabilization, i.e. a barrier to apoptosis induction. Over-expression of Bcl-2 and Bcl-xL is associated with tumor progression and may be responsible for drug resistance, making pro-survival Bcl-2 family members important targets for the development of anticancer agents. Pharmacological apoptosis modulation by manipulation of pro-apoptotic Bcl-2 family proteins, with the goal to treat disorders associated with uncontrolled cell death or to kill unwanted cells, is likely to represent an additional research focus in the coming years. The purpose of this review is to describe, with examples taken from recent patents, novel strategies for targeting the Bcl-2 family of apoptotic regulators through peptide-based approaches and selective delivery of functional nucleic acids.
Document Type: Research Article
Affiliations: IBCP, CNRS UMR 5086, 7 passage du Vercors, 69367 LYON Cedex France.
Publication date: 2007-02-01
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- Recent Patents on DNA and Gene Sequences publishes review articles by experts on recent patents on DNA and gene sequences. A selection of important and recent patents in the field is also included in the journal. The journal is essential reading for all researchers involved in applied molecular biology.