Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue/NC30, Cleveland, OH, 44195, USA.
Neuromolecular Med. 2019 Dec;21(4):484-492. doi: 10.1007/s12017-019-08550-w. Epub 2019 May 31.
Stroke significantly affects white matter in the brain by impairing axon function, which results in clinical deficits. Axonal mitochondria are highly dynamic and are transported via microtubules in the anterograde or retrograde direction, depending upon axonal energy demands. Recently, we reported that mitochondrial division inhibitor 1 (Mdivi-1) promotes axon function recovery by preventing mitochondrial fission only when applied during ischemia. Application of Mdivi-1 after injury failed to protect axon function. Interestingly, L-NIO, which is a NOS3 inhibitor, confers post-ischemic protection to axon function by attenuating mitochondrial fission and preserving mitochondrial motility via conserving levels of the microtubular adaptor protein Miro-2. We propose that preventing mitochondrial fission protects axon function during injury, but that restoration of mitochondrial motility is more important to promote axon function recovery after injury. Thus, Miro-2 may be a therapeutic molecular target for recovery following a stroke.
中风通过损害轴突功能显著影响大脑中的白质，从而导致临床缺损。轴突线粒体具有高度的动态性，并通过微管以顺行或逆行的方向运输，这取决于轴突的能量需求。最近，我们报道说，线粒体分裂抑制剂 1（Mdivi-1）仅在缺血期间应用时通过防止线粒体分裂来促进轴突功能的恢复。损伤后应用 Mdivi-1 无法保护轴突功能。有趣的是，NOS3 抑制剂 L-NIO 通过减轻线粒体分裂和通过维持微管接头蛋白 Miro-2 的水平来维持线粒体的运动性，从而对轴突功能提供缺血后保护。我们提出，在损伤期间，防止线粒体分裂可保护轴突功能，但恢复线粒体的运动性对于促进损伤后轴突功能的恢复更为重要。因此，Miro-2 可能是中风后恢复的治疗性分子靶标。
