New approaches and therapeutics targeting apoptosis in disease.
Apoptosis, the major form of cellular suicide, is central to various physiological processes and the maintenance of homeostasis in multicellular organisms. Presumably, even more important is a causative or contributing role of apoptosis to various human diseases. These include situations with unwanted cell accumulation (cancer) and failure to eradicate aberrant cells (autoimmune diseases) or disorders with an inappropriate loss of cells (heart failure, stroke, AIDS, neurodegenerative diseases, and liver injury). The past decade has witnessed a tremendous progress in the knowledge of the molecular mechanisms that regulate apoptosis and the mediators that either prevent or trigger cell death. Consequently, apoptosis regulators have emerged as key targets for the design of therapeutic strategies aimed at modulating cellular life-and-death decisions. Numerous novel approaches are currently being followed employing gene therapy and antisense strategies, recombinant biologics, or classical organic and combinatorial chemistry to target specific apoptotic regulators. Convincing proof-of-principle evidence obtained in several animal models confirms the validity of strategies targeting apoptosis and revealed an enormous potential for therapeutic intervention in a variety of illnesses. Although numerous apoptotic drugs are currently being developed, several therapeutics have progressed to clinical testing or are already approved and marketed. Here we review the recent progress of apoptosis-based therapies and survey some highlights in a very promising field of drug development.
Fischer
Ute
U
Institute of Molecular Medicine, University of Düsseldorf, Building 23.12, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
Schulze-Osthoff
Klaus
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D004194:Disease; D015195:Drug Design; D004358:Drug Therapy; D006801:Humans