The SARM1 Toll/Interleukin-1 Receptor Domain Possesses Intrinsic NAD+ Cleavage Activity that Promotes Pathological Axonal Degeneration

@article{Essuman2017TheST,
  title={The SARM1 Toll/Interleukin-1 Receptor Domain Possesses Intrinsic NAD+ Cleavage Activity that Promotes Pathological Axonal Degeneration},
  author={Kow Essuman and Daniel W. Summers and Yo Sasaki and Xianrong Mao and Aaron Diantonio and Jeffrey D. Milbrandt},
  journal={Neuron},
  year={2017},
  volume={93},
  pages={1334-1343.e5}
}
Axonal degeneration is an early and prominent feature of many neurological disorders. SARM1 is the central executioner of the axonal degeneration pathway that culminates in depletion of axonal NAD+, yet the identity of the underlying NAD+-depleting enzyme(s) is unknown. Here, in a series of experiments using purified proteins from mammalian cells, bacteria, and a cell-free protein translation system, we show that the SARM1-TIR domain itself has intrinsic NADase activity-cleaving NAD+ into ADP… CONTINUE READING
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