title: Modulating apoptosis as a target for effective therapy.
abstract: Alterations in cell proliferation and cell death are essential determinants in the pathogenesis and progression of several diseases such as cancer, neurodegenerative disorders or autoimmune diseases among others. Complex networks of regulatory factors determine whether cells proliferate or die. Recent progress in understanding the molecular changes offer the possibility of specifically targeting molecules and pathways to achieve more effective and rational therapies. Drugs that target molecules involved in apoptosis are used as treatment against several diseases. Candidates such as TNF death receptor family, caspase inhibitors, antagonists of the p53-MDM2 interaction, NF-kappaB and PI3K pathways and Bcl-2 family members have been targeted as cancer cell killing agents. Moreover, apoptosis of tumor cells can also be achieved by targeting the inhibitor of apoptosis proteins, IAPs, in addition to the classical antiproliferative approach. Disruption of STAT activation and interferon beta therapy have been used as a treatment to prevent the progression of some autoimmune diseases. In models of Parkinson's, Alzheimer's and amyotrophic lateral sclerosis, blocking of Par-4 expression or function, as well as caspase activation, prevents neuronal cell death. Finally, it has been shown that gene therapy may be an encouraging approach for treatment of neurodegenerative disorders.
authors.affiliation: Laboratoire d'Immunologie Cellulaire et Tissulaire, U543 INSERM, Hôpital Pitié Salpêtrière, Bâtiment CERVI, 83 Bd de 1'Hôpital, 75013 Paris, France.
authors.forename: Aarne
authors.initials: A
authors.lastname: Fleischer
authors.forename: Ata
authors.initials: A
authors.lastname: Ghadiri
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dessauge
authors.forename: Marianne
authors.initials: M
authors.lastname: Duhamel
authors.forename: Maria Paz
authors.initials: MP
authors.lastname: Rebollo
authors.forename: Fernando
authors.initials: F
authors.lastname: Alvarez-Franco
authors.forename: Angelita
authors.initials: A
authors.lastname: Rebollo
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015551:Autoimmunity; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology