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. 2010 Dec 22:8:31.
doi: 10.1186/1478-811X-8-31.

PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration

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PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration

Ganta Vijay Chaitanya et al. Cell Commun Signal. .

Abstract

The normal function of poly (ADP-ribose) polymerase-1 (PARP-1) is the routine repair of DNA damage by adding poly (ADP ribose) polymers in response to a variety of cellular stresses. Recently, it has become widely appreciated that PARP-1 also participates in diverse physiological and pathological functions from cell survival to several forms of cell death and has been implicated in gene transcription, immune responses, inflammation, learning, memory, synaptic functions, angiogenesis and aging. In the CNS, PARP inhibition attenuates injury in pathologies like cerebral ischemia, trauma and excitotoxicity demonstrating a central role of PARP-1 in these pathologies. PARP-1 is also a preferred substrate for several 'suicidal' proteases and the proteolytic action of suicidal proteases (caspases, calpains, cathepsins, granzymes and matrix metalloproteinases (MMPs)) on PARP-1 produces several specific proteolytic cleavage fragments with different molecular weights. These PARP-1 signature fragments are recognized biomarkers for specific patterns of protease activity in unique cell death programs. This review focuses on specific suicidal proteases active towards PARP-1 to generate signature PARP-1 fragments that can identify key proteases and particular forms of cell death involved in pathophysiology. The roles played by some of the PARP-1 fragments and their associated binding partners in the control of different forms of cell death are also discussed.

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Figures

Figure 1
Figure 1
PARP-1 interactions with cell death proteases. PARP-1 cleavage by various suicidal proteases like caspases, calpain, cathepsins and granzymes liberates fragments with specific molecular weights and are shown in this schematic representation. Importantly, 21-kD and 55-kD PARP-1 fragments generated by caspase 3/7 and Gra-A respectively function as an inhibitor of PARP-1 activity and might also play important roles in reducing necrosis and/or parthanatos. Further, PARP-1 and PARP-1 fragment's involvement in various forms of cell death e.g. autophagy, necrosis and parthanatos are also indicated.

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