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In light of the limited repertoire of therapeutical options available for the treatment of ischaemic stroke, the identification of novel potential targets is vital; in this respect, the present study demonstrates that the adaptor protein p66Shc holds this potential as an adjunct therapy to thrombolysis. Post-ischaemic silencing of p66Shc protein yielded beneficial effects in a mouse model of I/R brain injury underlying an interesting translational perspective for this target protein. Further, in proof-of-principle clinical experiments using PBMs, we demonstrate that p66Shc gene expression is transiently increased and that its levels correlate to short-term outcome in ischaemic stroke patients. Although these latter experiments are not directly relevant to the experiments performed in mice and in human endothelial cells, they provide novel important information about p66Shc regulation in stroke patients and set the basis for further investigations aimed at assessing the potential for p66Shc to become a novel therapeutic target as an adjunct of thrombolysis for the management of acute ischaemic stroke

In light of the limited repertoire of therapeutical options available for the treatment of ischaemic stroke, the identification of novel potential targets is vital; in this respect, the present study demonstrates that the adaptor protein p66Shc holds this potential as an adjunct therapy to thrombolysis. Post-ischaemic silencing of p66Shc protein yielded beneficial effects in a mouse model of I/R brain injury underlying an interesting translational perspective for this target protein. Further, in proof-of-principle clinical experiments using PBMs, we demonstrate that p66Shc gene expression is transiently increased and that its levels correlate to short-term outcome in ischaemic stroke patients. Although these latter experiments are not directly relevant to the experiments performed in mice and in human endothelial cells, they provide novel important information about p66Shc regulation in stroke patients and set the basis for further investigations aimed at assessing the potential for p66Shc to become a novel therapeutic target as an adjunct of thrombolysis for the management of acute ischaemic stroke