NeuroMolecular Medicine

, Volume 16, Issue 4, pp 787–798 | Cite as

Multiple Mechanisms of Iron-Induced Amyloid Beta-Peptide Accumulation in SHSY5Y Cells: Protective Action of Negletein

  • Priyanjalee Banerjee
  • Arghyadip Sahoo
  • Shruti Anand
  • Anirban Ganguly
  • Giuliana Righi
  • Paolo Bovicelli
  • Luciano Saso
  • Sasanka Chakrabarti
Original Paper


The increased accumulation of iron in the brain in Alzheimer’s disease (AD) is well documented, and excess iron is strongly implicated in the pathogenesis of the disease. The adverse effects of accumulated iron in AD brain may include the oxidative stress, altered amyloid beta-metabolism and the augmented toxicity of metal-bound amyloid beta 42. In this study, we have shown that exogenously added iron in the form of ferric ammonium citrate (FAC) leads to considerable accumulation of amyloid precursor protein (APP) without a corresponding change in the concerned gene expression in cultured SHSY5Y cells during exposure up to 48 h. This phenomenon is also associated with increased β-secretase activity and augmented release of amyloid beta 42 in the medium. Further, the increase in β-secretase activity, in SHSY5Y cells, upon exposure to iron apparently involves reactive oxygen species (ROS) and NF-κB activation. The synthetic flavone negletein (5,6-dihydroxy-7-methoxyflavone), which is a known chelator for iron, can significantly prevent the effects of FAC on APP metabolism in SHSY5Y cells. Further, this compound inhibits the iron-dependent formation of ROS and also blocks the iron-induced oligomerization of amyloid beta 42 in vitro. In concentrations used in this study, negletein alone appears to have only marginal toxic effects on cell viability, but, on the other hand, the drug is capable of ameliorating the iron-induced loss of cell viability considerably. Our results provide the initial evidence of potential therapeutic effects of negletein, which should be explored in suitable animal models of AD.


Alzheimer’s disease Amyloid beta 42 β-Secretase Flavone Iron 



The work was supported by a Grant from Department of Biotechnology, Govt. of India, New Delhi. PB was supported by a Senior Research Fellowship from Department of Science and Technology, Govt. of India, New Delhi.

Conflict of interest

The authors have no conflict of interests.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Priyanjalee Banerjee
    • 1
  • Arghyadip Sahoo
    • 1
  • Shruti Anand
    • 1
  • Anirban Ganguly
    • 1
  • Giuliana Righi
    • 2
  • Paolo Bovicelli
    • 2
  • Luciano Saso
    • 3
  • Sasanka Chakrabarti
    • 1
  1. 1.Department of BiochemistryInstitute of Postgraduate Medical Education and ResearchKolkataIndia
  2. 2.CNR ICB-Unity of Rome, c/o Department of ChemistrySapienza University of RomeRomeItaly
  3. 3.Department of Physiology and Pharmacology, Vittorio ErspamerSapienza University of RomeRomeItaly

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