Abstract: The Keystone Symposium on Apoptotic and Non‐Apoptotic Cell Death Pathways took place between 15 and 20 April 2007, in Monterey, CA, USA, and was organized by J. Yuan, D. Bredesen and Z. Zakeri.
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In an adult human, millions of cells die each second as a result of normal development as well as loss associated with pathology. For years, it has been widely assumed that this cell death occurs primarily through one mechanism—apoptosis—at least in physiological circumstances (Lockshin & Zakeri, 2001; Horvitz, 2003). The 2007 Keystone Symposium on Apoptosis and Non‐Apoptotic Cell Death Pathways marked a turning point in the field by acknowledging the multiplicity of cell death mechanisms that exist. In most systems of apoptosis induction, the inhibition of caspases—cysteine proteases that are crucial to apoptosis—unmasks other mechanisms of cell death, which often shifts the apoptotic default pathway to non‐apoptotic cell death modalities. Furthermore, such non‐apoptotic cell death mechanisms occur in several in vitro and in vivo models of normal and pathological cell death (Yuan, 2003; Levine & Klionsky, 2004; Festjens et al , 2006; Gozuacik & Kimchi, 2007).
The length of time that it has taken for these non‐apoptotic cell deaths to be fully accepted reflects the importance and impact of the initial discovery of apoptosis and its caspase‐mediated mechanism. It might also reflect a certain reluctance at recognizing—even down one's own microscope—the existence of pathways that do not fit the established dogma. Meetings such as this symposium do much for the realization of the widespread occurrence of non‐apoptotic cell death, and this should have therapeutic consequences.
The terms ‘programmed cell death’ and ‘apoptosis’ have been virtually synonymous for more than two decades. However, programmed cell death encompasses the cellular demise that results from an ordered, controlled process irrespective of the mechanism, whereas apoptosis describes …
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