Mitochondria! Dynamics Decrease Prior to Axon Degeneration Induced by Vincristine and are Partially Rescued by Overexpressed cytNmnatl

作者：Berbusse Gregory W; Woods Laken C; Vohra Bhupinder P S; Naylor Kari^*

来源：Frontiers in Cellular Neuroscience, 2016, 10: 179.

DOI：10.3389/fncel.2016.00179

• neurodegeneration
• mitochondria
• Nmnat
• fission
• fusion
• vincristine

Axon degeneration is a prominent feature of various neurodegenerative diseases, such as Parkinson's and Alzheimer's, and is often characterized by aberrant mitochondria' dynamics. Mitochondria' fission, fusion, and motility have been shown to be particularly important in progressive neurodegeneration. Thus we investigated these imperative dynamics, as well as mitochondria' fragmentation in vincristine induced axon degradation in cultured dorsal root ganglia (DRG) neurons. CytNmnatl inhibits axon degeneration in various paradigms including vincristine toxicity. The mechanism of its protection is not yet fully understood: therefore, we also investigated the effect of cytNmnatl on mitochondria' dynamics in vincristine treated neurons. We observed that vincristine treatment decreases the rate of mitochondria' fission, fusion and motility and induces mitochondria' fragmentation. These mitochondria' events precede visible axon degeneration. Overexpression of cytNmnatl inhibits axon degeneration and preserves the normal mitochondria' dynamics and motility in vincristine treated neurons. We suggest the alterations in mitochondria' structure and dynamics are early events which lead to axon degeneration and cytNmnatl blocks axon degeneration by halting the vincristine induced changes to mitochondria' structure and dynamics.

• 出版日期2016-7-19