William Jewell College, Department of Biology, Liberty, MO, USA.
William Jewell College, Department of Biology, Liberty, MO, USA.
Neurochem Int. 2018 Dec;121:86-97. doi: 10.1016/j.neuint.2018.09.010. Epub 2018 Sep 29.
Golgi fragmentation and loss of Nicotinamide Mononucleotide Adenylyltransferase 2 (NMNAT2) are the early key features of many neurodegenerative disorders. We investigated the link between NMNAT2 loss, Golgi fragmentation and axon degeneration. Golgi fragmentation in the cultured dorsal root ganglion (DRG) neurons resulted in caspase dependent axon degeneration and neuronal cell death. NMNAT2 depletion in the DRG neurons caused Golgi fragmentation and caspase dependent axon degeneration. NMNAT2 depletion did not cause ATP loss in the axons. These results indicate that NMNAT2 is required for maintenance of Golgi structure. Loss of Golgi structure or Nmnat2 depletion causes caspase dependent neurodegeneration. cytNmnat1 overexpression inhibited the axon degeneration induced by Golgi fragmentation or NMNAT2 depletion. These results also suggest that these degeneration signals converge on a common cytNmnat1 mediated axon protective program and are distinct from the SARM1 mediated caspase independent axon degeneration.
高尔基复合体碎片化和烟酰胺单核苷酸腺嘌呤二核苷酸转移酶 2（NMNAT2）的丢失是许多神经退行性疾病的早期关键特征。我们研究了 NMNAT2 丢失、高尔基复合体碎片化和轴突退化之间的联系。培养的背根神经节（DRG）神经元中的高尔基复合体碎片化导致半胱天冬酶依赖性轴突退化和神经元细胞死亡。DRG 神经元中的 NMNAT2 耗竭导致高尔基复合体碎片化和半胱天冬酶依赖性轴突退化。NMNAT2 耗竭不会导致轴突中 ATP 的丢失。这些结果表明 NMNAT2 是维持高尔基复合体结构所必需的。高尔基复合体结构的丢失或 Nmnat2 耗竭会导致半胱天冬酶依赖性神经退行性变。cytNmnat1 的过表达抑制了高尔基复合体碎片化或 NMNAT2 耗竭诱导的轴突退化。这些结果还表明，这些退化信号汇集到一个共同的 cytNmnat1 介导的轴突保护程序中，与 SARM1 介导的半胱天冬酶非依赖性轴突退化不同。
