1] School of Biomedical Sciences, University of Nottingham, Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK. [2].
1] The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, CB22 3AT, UK. [2].
Nat Rev Neurosci. 2014 Jun;15(6):394-409. doi: 10.1038/nrn3680.
Axon degeneration is a prominent early feature of most neurodegenerative disorders and can also be induced directly by nerve injury in a process known as Wallerian degeneration. The discovery of genetic mutations that delay Wallerian degeneration has provided insight into mechanisms underlying axon degeneration in disease. Rapid Wallerian degeneration requires the pro-degenerative molecules SARM1 and PHR1. Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is essential for axon growth and survival. Its loss from injured axons may activate Wallerian degeneration, whereas NMNAT overexpression rescues axons from degeneration. Here, we discuss the roles of these and other proposed regulators of Wallerian degeneration, new opportunities for understanding disease mechanisms and intriguing links between Wallerian degeneration, innate immunity, synaptic growth and cell death.
轴突变性是大多数神经退行性疾病的一个突出的早期特征，也可以通过称为沃勒氏变性的过程直接由神经损伤诱导。发现延迟沃勒氏变性的遗传突变为疾病中轴突变性的机制提供了深入了解。快速沃勒氏变性需要促退化分子 SARM1 和 PHR1。烟酰胺单核苷酸腺苷酰转移酶 2 (NMNAT2) 对轴突生长和存活至关重要。其从损伤的轴突中丢失可能会激活沃勒氏变性，而 NMNAT 的过表达则可以挽救轴突免于变性。在这里，我们讨论了这些和其他被提议的沃勒氏变性调节剂的作用，这为理解疾病机制提供了新的机会，并且还揭示了沃勒氏变性、先天免疫、突触生长和细胞死亡之间的有趣联系。
