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Post‐ischemic brain damage: targeting PARP‐1 within the ischemic neurovascular units as a realistic avenue to stroke treatment
Author(s) -
Moroni Flavio,
Chiarugi Alberto
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06768.x
Subject(s) - neurovascular bundle , neuroprotection , stroke (engine) , medicine , poly adp ribose polymerase , neurodegeneration , effector , ischemia , neuroscience , programmed cell death , clinical trial , pharmacology , bioinformatics , apoptosis , polymerase , pathology , biology , immunology , disease , enzyme , mechanical engineering , biochemistry , engineering
Stroke is the third leading cause of death in industrialized countries but efficacious stroke treatment is still an unmet need. Preclinical research indicates that different molecules afford protection from ischemic neurodegeneration, but all clinical trials conducted so far have inexorably failed. Critical re‐evaluation of experimental data shows that all the components of the neurovascular unit, such as neurons, glia, endothelia and basal membranes, must be protected during the ischemic insult to obtain substantial and long‐lasting neuroprotection. Here, we propose the nuclear enzyme poly(ADP‐ribose) polymerase (PARP‐1) as a key effector of cell death in the various elements of the neurovascular units, and assert that drugs inhibiting PARP‐1 may therefore represent valuable tools for pharmacological treatment of stroke patients.