Saxena Smita, Caroni Pico
Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Prog Neurobiol. 2007 Oct;83(3):174-91. doi: 10.1016/j.pneurobio.2007.07.007. Epub 2007 Aug 2.
Axon degeneration is an active, tightly controlled and versatile process of axon segment self-destruction. Although not involving cell death, it resembles apoptosis in its logics. It involves three distinct steps: induction of competence in specific neurons, triggering of degeneration at defined axon segments of competent neurons, and rapid fragmentation and removal of the segments. The mechanisms that initiate degeneration are specific to individual settings, but the final pathway of pruning is shared; it involves microtubule disassembly, axon swellings, axon fragmentation, and removal of the remnants by locally recruited phagocytes. The tight regulatory properties of axon degeneration distinguish it from passive loss phenomena, and confer significance to processes that involve it. Axon degeneration has prominent roles in development, upon lesions and in disease. In development, it couples the progressive specification of neurons and circuits to the removal of defined axon branches. Competence might involve transcriptional switches, and local triggering can involve axon guidance molecules and synaptic activity patterns. Lesion-induced Wallerian degeneration is inhibited in the presence of Wld(S) fusion protein in neurons; it involves early local, and later, distal degeneration. It has recently become clear that like in other settings, axon degeneration in disease is a rapid and specific process, which should not be confused with a variety of disease-related pathologies. Elucidating the specific mechanisms that initiate axon degeneration should open up new avenues to investigate principles of circuit assembly and plasticity, to uncover mechanisms of disease progression, and to identify ways of protecting synapses and axons in disease.
轴突退化是一个活跃的、受到严格调控且具有多种形式的轴突节段自我破坏过程。尽管不涉及细胞死亡，但其逻辑与细胞凋亡相似。它包括三个不同的步骤：在特定神经元中诱导能力，在有能力的神经元的特定轴突节段触发退化，以及快速碎片化并清除这些节段。引发退化的机制因具体情况而异，但修剪的最终途径是相同的；它涉及微管解聚、轴突肿胀、轴突碎片化以及由局部募集的吞噬细胞清除残余物。轴突退化的严格调控特性使其有别于被动性损失现象，并赋予涉及它的过程以重要意义。轴突退化在发育、损伤和疾病中都起着重要作用。在发育过程中，它将神经元和神经回路的逐步特化与特定轴突分支的清除联系起来。能力诱导可能涉及转录开关，而局部触发可能涉及轴突导向分子和突触活动模式。在神经元中存在Wld(S)融合蛋白时，损伤诱导的华勒氏变性会受到抑制；它涉及早期局部和后期的远端退化。最近已经明确，与其他情况一样，疾病中的轴突退化是一个快速且特定的过程，不应与各种疾病相关的病理变化相混淆。阐明引发轴突退化的具体机制应该会为研究神经回路组装和可塑性的原理、揭示疾病进展机制以及确定在疾病中保护突触和轴突的方法开辟新途径。
