Neddylation dysfunction in Alzheimer's disease

Ubiquitin‐dependent proteolysis is a major mechanism that downregulates misfolded proteins or those that have finished a programmed task. In the last two decades, neddylation has emerged as a major regulatory pathway for ubiquitination. Central to the neddylation pathway is the amyloid precursor protein ( APP )‐binding protein APP ‐ BP 1, which together with Uba3, plays an analogous role to the ubiquitin‐activating enzyme E1 in nedd8 activation. Activated nedd8 covalently modifies and activates a major class of ubiquitin ligases called Cullin‐ RING ligases ( CRL s). New evidence suggests that neddylation also modifies Type‐1 transmembrane receptors such as APP . Here we review the functions of neddylation and summarize evidence suggesting that dysfunction of neddylation is involved in Alzheimer's disease.