Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Trends Mol Med. 2010 Apr;16(4):160-70. doi: 10.1016/j.molmed.2010.02.002. Epub 2010 Mar 6.
Axonal degeneration causes morbidity in many neurological conditions including stroke, neurotrauma and multiple sclerosis. The limited ability of central nervous system (CNS) neurons to regenerate, combined with the observation that axonal damage causes clinical disability, has spurred efforts to investigate the mechanisms of axonal degeneration. Ca influx from outside the axon is a key mediator of injury. More recently, substantial pools of intra-axonal Ca sequestered in the 'axoplasmic reticulum' have been reported. These Ca stores are under the control of multimolecular 'nanocomplexes' located along the internodes under the myelin. The overactivation of these complexes during disease can lead to a lethal release of Ca from intra-axonal stores. Rich receptor pharmacology offers tantalizing therapeutic options targeting these nanocomplexes in the many diseases where axonal degeneration is prominent.
轴突变性会导致许多神经疾病的发病，包括中风、神经创伤和多发性硬化症。中枢神经系统（CNS）神经元的再生能力有限，加上轴突损伤会导致临床残疾的观察结果，这促使人们努力研究轴突变性的机制。来自轴突外部的钙流入是损伤的关键介质。最近，大量存在于“轴浆内质网”中的轴内钙池已被报道。这些钙库受位于髓鞘下节段内的多分子“纳米复合物”的控制。在疾病期间，这些复合物的过度激活可能导致轴内储存的钙致命释放。丰富的受体药理学为许多轴突变性明显的疾病中针对这些纳米复合物的治疗提供了诱人的选择。
