|  Help  |  About  |  Contact Us

Publication : SARM1 acts downstream of neuroinflammatory and necroptotic signaling to induce axon degeneration.

First Author  Ko KW Year  2020
Journal  J Cell Biol Volume  219
Issue  8 PubMed ID  32609299
Mgi Jnum  J:305854 Mgi Id  MGI:6706123
Doi  10.1083/jcb.201912047 Citation  Ko KW, et al. (2020) SARM1 acts downstream of neuroinflammatory and necroptotic signaling to induce axon degeneration. J Cell Biol 219(8)
abstractText  Neuroinflammation and necroptosis are major contributors to neurodegenerative disease, and axon dysfunction and degeneration is often an initiating event. SARM1 is the central executioner of pathological axon degeneration. Here, we demonstrate functional and mechanistic links among these three pro-degenerative processes. In a neuroinflammatory model of glaucoma, TNF-alpha induces SARM1-dependent axon degeneration, oligodendrocyte loss, and subsequent retinal ganglion cell death. TNF-alpha also triggers SARM1-dependent axon degeneration in sensory neurons via a noncanonical necroptotic signaling mechanism. MLKL is the final executioner of canonical necroptosis; however, in axonal necroptosis, MLKL does not directly trigger degeneration. Instead, MLKL induces loss of the axon survival factors NMNAT2 and STMN2 to activate SARM1 NADase activity, which leads to calcium influx and axon degeneration. Hence, these findings define a specialized form of axonal necroptosis. The demonstration that neuroinflammatory signals and necroptosis can act locally in the axon to stimulate SARM1-dependent axon degeneration identifies a therapeutically targetable mechanism by which neuroinflammation can stimulate axon loss in neurodegenerative disease.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

3 Bio Entities

Trail: Publication

0 Expression