Neuronal SEL1L-HRD1 ERAD regulates one-carbon metabolism and is essential for motor function and survival.

ABSTRACT: Hypomorphic variants in the SEL1L-HRD1 ER-associated degradation (ERAD) complex have been linked to severe neurological syndromes in children, including neurodevelopmental delay, intellectual disability, motor dysfunction, and early death. Despite this association, its physiological importance and underlying mechanisms in neurons remain poorly understood. Here, we show that neuronal SEL1L-HRD1 ERAD is essential for maintaining one-carbon metabolism, motor function, and overall viability. Neuron-specific deletion of Sel1L in mice (Sel1L ^SynCre ) resulted in growth retardation, severe motor impairments, and early mortality by 9 weeks of age-mirroring core clinical features observed in affected patients-despite preserved neuronal numbers and only modest ER stre

SUBMITTER: Torres M 

PROVIDER: S-EPMC12262411 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature