• Open Access

Neddylation dysfunction in Alzheimer's disease

Authors

  • Yuzhi Chen,

    Corresponding author
    1. Department of Geriatrics and Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    • Correspondence to: Dr. Y. CHEN, Department of Geriatrics, Slot 807, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

      Tel.: 501-526-5805

      Fax: 501-526-5830

      E-mail: chenyuzhi@uams.edu

    Search for more papers by this author
  • Rachael L. Neve,

    1. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA
    Search for more papers by this author
  • Helena Liu

    1. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
    Search for more papers by this author

Abstract

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.

Ancillary