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-BP1, 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 (CRLs). 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.
Department of Geriatrics and Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. chenyuzhi@uams.edu
Yuzhi
Y
Chen
Rachael L
RL
Neve
Helena
H
Liu
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D044842:Cullin Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D000075687:NEDD8 Protein; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism; D054875:Ubiquitination; D014452:Ubiquitins / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; C486317:CAND1 protein, human; C100318:Cullin 1; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D014157:Transcription Factors; D014452:Ubiquitins; D046988:Proteasome Endopeptidase Complex; D044764:Ubiquitin-Activating Enzymes; C491802:NAE protein, human