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13.
Reduced risk of apoptosis : mechanisms of stress responses
Milisav, Irina ; Poljšak, Borut, 1976- ; Ribarič, Samo
Apoptosis signaling pathways are integrated into a wider network of interconnected apoptotic and anti- apoptotic pathways that regulate a broad range of cell responses from cell death to growth, ...development and stress responses. An important trigger for anti- or pro- apoptotic cell responses are diferent forms of stress includ - ing hypoxia, energy deprivation, DNA damage or inlam - mation. Stress duration and intensity determine whether the cell's response will be improved cell survival, due to stress adaptation, or cell death by apoptosis, necrosis or autophagy. Although the interplay between enhanced stress tolerance and modulation of apoptosis triggering is not yet fully understood, there is a substantial body of experimen - tal evidence demonstrating that apoptosis and anti-apop - tosis signaling pathways can be manipulated to trigger or delay apoptosis in vitro or in vivo. Anti-apoptotic strate - gies cover a broad range of approaches. These interventions include mediators that prevent apoptosis (trophic factors and cytokines), apoptosis inhibition (caspase inhibition, stimulation of anti-apoptotic or inhibition of pro-apoptotic proteins and elimination of apoptotic stimulus), adaptive stress responses (induction of maintenance and repair, caspase inactivation) and cell-cell interactions (blocking engulfment and modiied micro environment). There is a consensus that preclinical eicacy and safety evaluations of anti-apoptotic strategies should be performed with proto - cols that simulate as closely as possible the efects of aging, gender, risk factors, comorbidities and co-medications.
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