Abstract
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.
MeSH terms
-
Brain Damage, Chronic / drug therapy
-
Brain Damage, Chronic / etiology
-
Brain Damage, Chronic / genetics
-
Brain Damage, Chronic / pathology*
-
Brain Ischemia / complications*
-
Brain Ischemia / drug therapy
-
Brain Ischemia / genetics
-
Brain Ischemia / pathology*
-
Cell Death
-
Cerebrovascular Circulation
-
Clinical Trials as Topic
-
Collateral Circulation
-
Humans
-
Neurons / pathology*
-
Neuroprotective Agents / therapeutic use
-
Poly (ADP-Ribose) Polymerase-1
-
Poly(ADP-ribose) Polymerase Inhibitors
-
Poly(ADP-ribose) Polymerases / drug effects
-
Poly(ADP-ribose) Polymerases / physiology*
-
Receptors, N-Methyl-D-Aspartate / physiology
-
Stroke / drug therapy*
-
Stroke / pathology*
-
Transcriptional Activation
Substances
-
Neuroprotective Agents
-
Poly(ADP-ribose) Polymerase Inhibitors
-
Receptors, N-Methyl-D-Aspartate
-
PARP1 protein, human
-
Poly (ADP-Ribose) Polymerase-1
-
Poly(ADP-ribose) Polymerases