NEDD8-activating enzyme E1 regulatory subunit

NAE1 (NEDD8-activating enzyme E1 regulatory subunit) is the regulatory component of the dimeric E1 enzyme that activates NEDD8, a ubiquitin-like protein modifier (UniProt: Q13564). NAE1 catalyzes the adenylation and transfer of NEDD8 to downstream ubiquitin-like conjugation machinery, a process called neddylation that regulates cell cycle progression, growth, viability, and development.

NAE1 is expressed broadly and participates in protein post-translational modification pathways central to cell cycle control. Beyond AD, NAE1 mutations are associated with neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia (NEDFIH, MIM 620210), an autosomal recessive condition characterized by developmental delay, facial dysmorphism, and neuroimaging abnormalities including white matter changes and ventricular enlargement (UniProt: Q13564).

NAE1 is upregulated in Alzheimer's disease brain tissue compared to age-matched controls (mean log2 fold-change +0.95; Chaparral AD proteomics). This elevation in a key neddylation enzyme may reflect altered ubiquitin-like signaling in AD pathology, though the functional significance requires further investigation.