Open AccessSARM1 participates in axonal degeneration and mitochondrial dysfunction in prion disease
Author(s) -
Xiangmei Zhou,
Lifeng Yang,
Mengyu Lai,
Jie Li,
Xi-Xi Zhang,
Wei Wu,
Zhiping Li,
Zhixin Sun,
Mengyang Zhao,
Dongming Yang,
Dongdong Wang,
Wen Li,
Deming Zhao
Publication year - 2022
Publication title -
neural regeneration research/neural regeneration research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.93
H-Index - 38
eISSN - 1876-7958
pISSN - 1673-5374
DOI - 10.4103/1673-5374.337051
Subject(s) - neurodegeneration , degeneration (medical) , mitochondrion , apoptosis , nad+ kinase , axonal degeneration , mutation , biology , wallerian degeneration , microbiology and biotechnology , pathology , neuroscience , medicine , disease , biochemistry , gene , enzyme
Prion disease represents a group of fatal neurogenerative diseases in humans and animals that are associated with energy loss, axonal degeneration, and mitochondrial dysfunction. Axonal degeneration is an early hallmark of neurodegeneration and is triggered by SARM1. We found that depletion or dysfunctional mutation of SARM1 protected against NAD + loss, axonal degeneration, and mitochondrial functional disorder induced by the neurotoxic peptide PrP 106-126 . NAD + supplementation rescued prion-triggered axonal degeneration and mitochondrial dysfunction and SARM1 overexpression suppressed this protective effect. NAD + supplementation in PrP 106-126 -incubated N2a cells, SARM1 depletion, and SARM1 dysfunctional mutation each blocked neuronal apoptosis and increased cell survival. Our results indicate that the axonal degeneration and mitochondrial dysfunction triggered by PrP 106-126 are partially dependent on SARM1 NADase activity. This pathway has potential as a therapeutic target in the early stages of prion disease.