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- W3081881569 abstract "ABSTRACT Sterile alpha and toll/interleukin receptor (TIR) motif–containing protein 1 (SARM1) is a neuronally expressed NAD + glycohydrolase whose activity is increased in response to various stressors. The consequent depletion of NAD + triggers axonal degeneration (i.e., Wallerian degeneration), which is a characteristic feature of neurological diseases, including peripheral neuropathies and traumatic brain injury. Notably, SARM1 knockout mice show minimal degeneration in models of peripheral neuropathy and traumatic brain injury, making SARM1 a promising therapeutic target. However, the development of SARM1 inhibitors has been challenging as the purified enzyme is largely inactive. Herein, we report that SARM1 activity is increased ∼2000–fold by a liquid-to-solid phase transition. These findings provide critical insights into SARM1 biochemistry with important implications for the situation in vivo . Moreover, they will facilitate the discovery of novel SARM1–targeted therapeutics. Graphical Abstract" @default.
- W3081881569 created "2020-09-08" @default.
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- W3081881569 date "2020-08-29" @default.
- W3081881569 modified "2023-10-03" @default.
- W3081881569 title "A Liquid-to-Solid Phase Transition Enhances the Catalytic Activity of SARM1" @default.
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- W3081881569 doi "https://doi.org/10.1101/2020.08.28.272377" @default.
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