This review summarizes recent progress in understanding the role of p53-upregulated mediator
of apoptosis (PUMA) in molecular pathways with respect to its potential therapeutic applications.
Particular emphasis is given to the PUMA´s role in ionizing radiation-induced signalling as radiotoxicity
of normal tissue is mediated mostly via apoptosis. PUMA and its p53-dependent and p53-
independent induction are described and potential use as a new target for the development of radioprotective
agents is suggested. Further implications, including targeting PUMA to prevent and treat cardiovascular
and neurodegenerative diseases, are also discussed together with an overview of other
therapeutic applications. Finally, basic chemical structures for the development of novel PUMA
modulators such as pifithrine derivatives, kinase inhibitors or modulators of Bcl-2 protein family are
Keywords: PUMA, ionizing radiation, small molecule inhibitor, radioprotection, hearth, brain.
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