Preventing TAB1-mediated p38 activation during myocardial infarction

在心肌梗塞期间，一种叫做p38的酶被激活，使心脏受到的损伤恶化。虽然药物可以抑制p38，从而减少心脏损伤，但这些药物在早期临床试验中产生了严重的副作用。这可能是因为p38在人体中是一种非常重要的酶。这项拨款的目的是通过干扰p38被激活的方式，找到一种在心肌梗死期间抑制p38的方法。之所以吸引人是因为心肌梗死期间的激活机制非常不寻常，因为它需要p38结合另一种称为TAB1的蛋白质。因此，在其他情况下，干扰这一机制不应抑制p38的激活。

During myocardial infarction an enzyme called p38 becomes activated and worsens the injury suffered by the heart. Although p38 can be inhibited with drugs, and this leads to reduced heart injury, these drugs have caused serious side effects in early clinical trials. This is probably because p38 is a very important enzyme throughout the body. The purpose of this grant is to find a way of inhibiting p38 during myocardial infarction by interfering with the way it becomes activated. The reason why this is attractive is that the activation mechanism during myocardial infarction is very unusual in that it requires p38 to bind another protein called TAB1. Thus interfering with this mechanism should not inhibit p38 activation under other circumstances.