Moroni Flavio, Chiarugi Alberto
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
FEBS J. 2009 Jan;276(1):36-45. doi: 10.1111/j.1742-4658.2008.06768.x.
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.
中风是工业化国家中第三大致死原因，但有效的中风治疗仍是未被满足的需求。临床前研究表明，不同分子可提供针对缺血性神经变性的保护作用，但迄今为止进行的所有临床试验均不可避免地失败了。对实验数据的关键重新评估表明，在缺血性损伤期间，神经血管单元的所有组成部分，如神经元、神经胶质细胞、内皮细胞和基底膜，都必须得到保护，以获得实质性和持久的神经保护作用。在此，我们提出核酶聚（ADP-核糖）聚合酶（PARP-1）是神经血管单元各组成部分细胞死亡的关键效应因子，并断言抑制PARP-1的药物可能因此成为中风患者药物治疗的有价值工具。
