• FKBP12 regulates the localization and processing of amyloid precursor protein in human cell lines

    • Fulltext

       

        Click here to view fulltext PDF


      Permanent link:
      https://www.ias.ac.in/article/fulltext/jbsc/039/01/0085-0095

    • Keywords

       

      AICD (APP intracellular domain); Alzheimer’s disease; FK506; FKBPs

    • Abstract

       

      One of the pathological hallmarks of Alzheimer’s disease is the presence of insoluble extracellular amyloid plaques. These plaques are mainly constituted of amyloid beta peptide (A𝛽), a proteolytic product of amyloid precursor protein (APP). APP processing also generates the APP intracellular domain (AICD). We have previously demonstrated that AICD interacts with FKBP12, a peptidyl-prolyl cis-trans isomerase (PPIase) ubiquitous in nerve systems. This interaction was interfered by FK506, a clinically used immunosuppressant that has recently been reported to be neuroprotective. To elucidate the roles of FKBP12 in the pathogenesis of Alzheimer’s disease, the effect of FKBP12 overexpression on APP processing was evaluated. Our results revealed that APP processing was shifted towards the amyloidogenic pathway, accompanied by a change in the subcellular localization of APP, upon FKBP12 overexpression. This FKBP12-overexpression-induced effect was reverted by FK506. These findings support our hypothesis that FKBP12 may participate in the regulation of APP processing. FKBP12 overexpression may lead to the stabilization of a certain isomer (presumably the cis form) of the Thr668-Pro669 peptide bond in AICD, therefore change its affinity to flotillin-1 or other raft-associated proteins, and eventually change the localization pattern and cause a shift in the proteolytic processing of APP.

    • Author Affiliations

       

      Fan-Lun Liu1 Ting-Yi Liu1 Fan-Lu Kung1 2

      1. School of Pharmacy, National Taiwan University, Taipei 10051( Taiwan, R.O.C.
      2. Graduate Institute of Brain and Mind Sciences, National Taiwan University, Taipei 10051( Taiwan, R.O.C
    • Dates

       
  • Journal of Biosciences | News

    • Editorial Note on Continuous Article Publication

      Posted on July 25, 2019

      Click here for Editorial Note on CAP Mode

© 2017-2019 Indian Academy of Sciences, Bengaluru.