Ontology highlight
ABSTRACT:
SUBMITTER: Dingwall CB
PROVIDER: S-EPMC9711884 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Dingwall Caitlin B CB Strickland Amy A Yum Sabrina W SW Yim Aldrin Ky AK Zhu Jian J Wang Peter L PL Yamada Yurie Y Schmidt Robert E RE Sasaki Yo Y Bloom A Joseph AJ DiAntonio Aaron A Milbrandt Jeffrey J
The Journal of clinical investigation 20221201 23
Axon loss contributes to many common neurodegenerative disorders. In healthy axons, the axon survival factor NMNAT2 inhibits SARM1, the central executioner of programmed axon degeneration. We identified 2 rare NMNAT2 missense variants in 2 brothers afflicted with a progressive neuropathy syndrome. The polymorphisms resulted in amino acid substitutions V98M and R232Q, which reduced NMNAT2 NAD+-synthetase activity. We generated a mouse model to mirror the human syndrome and found that Nmnat2V98M/R ...[more]