The SARM1 axon degeneration pathway: control of the NAD+ metabolome regulates axon survival in health and disease
MD Figley, A DiAntonio - Current opinion in neurobiology, 2020 - Elsevier
Current opinion in neurobiology, 2020•Elsevier
Highlights•A mechanistic understanding of the endogenous axon degeneration pathway has
emerged over the past few years.•Axonal health is maintained by a balance of survival
factors NMNAT2 and STMN2 and pro-degenerative molecules DLK and SARM1.•SARM1
promotes axon death via NAD+ cleavage and is the founding member of the TIR-domain
family of NAD+-consuming enzymes.•The endogenous axon degeneration pathway is
activated in many neurodegenerative conditions and can be targeted for therapy.Axons are …
emerged over the past few years.•Axonal health is maintained by a balance of survival
factors NMNAT2 and STMN2 and pro-degenerative molecules DLK and SARM1.•SARM1
promotes axon death via NAD+ cleavage and is the founding member of the TIR-domain
family of NAD+-consuming enzymes.•The endogenous axon degeneration pathway is
activated in many neurodegenerative conditions and can be targeted for therapy.Axons are …
Highlights
- A mechanistic understanding of the endogenous axon degeneration pathway has emerged over the past few years.
- Axonal health is maintained by a balance of survival factors NMNAT2 and STMN2 and pro-degenerative molecules DLK and SARM1.
- SARM1 promotes axon death via NAD+ cleavage and is the founding member of the TIR-domain family of NAD+-consuming enzymes.
- The endogenous axon degeneration pathway is activated in many neurodegenerative conditions and can be targeted for therapy.
Axons are essential for nervous system function and axonal pathology is a common hallmark of many neurodegenerative diseases. Over a century and a half after the original description of Wallerian axon degeneration, advances over the past five years have heralded the emergence of a comprehensive, mechanistic model of an endogenous axon degenerative process that can be activated by both injury and disease. Axonal integrity is maintained by the opposing actions of the survival factors NMNAT2 and STMN2 and pro-degenerative molecules DLK and SARM1. The balance between axon survival and self-destruction is intimately tied to axonal NAD+ metabolism. These mechanistic insights may enable axon-protective therapies for a variety of human neurodegenerative diseases including peripheral neuropathy, traumatic brain injury and potentially ALS and Parkinson’s.
Elsevier
