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Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease

Journal Article


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Abstract


  • Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, yet current

    therapeutic treatments are inadequate due to a complex disease pathogenesis. The plant polyphenol

    apigenin has been shown to have anti-inflammatory and neuroprotective properties in a number of

    cell and animal models; however a comprehensive assessment has not been performed in a human

    model of AD. Here we have used a human induced pluripotent stem cell (iPSC) model of familial and

    sporadic AD, in addition to healthy controls, to assess the neuroprotective activity of apigenin. The

    iPSC-derived AD neurons demonstrated a hyper-excitable calcium signalling phenotype, elevated levels

    of nitrite, increased cytotoxicity and apoptosis, reduced neurite length and increased susceptibility to

    inflammatory stress challenge from activated murine microglia, in comparison to control neurons. We

    identified that apigenin has potent anti-inflammatory properties with the ability to protect neurites

    and cell viability by promoting a global down-regulation of cytokine and nitric oxide (NO) release in

    inflammatory cells. In addition, we show that apigenin is able to protect iPSC-derived AD neurons

    via multiple means by reducing the frequency of spontaneous Ca2+ signals and significantly reducing

    caspase-3/7 mediated apoptosis. These data demonstrate the broad neuroprotective action of apigenin

    against AD pathogenesis in a human disease model.

Authors


  •   Balez, Rachelle (external author)
  •   Steiner, Nicole (external author)
  •   Engel, Martin
  •   Sanz Munoz, Sonia (external author)
  •   Lum, Jeremy
  •   Wu, Yizhen (external author)
  •   Wang, Dadong (external author)
  •   Vallotton, Pascal (external author)
  •   Sachdev, Perminder (external author)
  •   O'Connor, Michael D. (external author)
  •   Sidhu, Kuldip (external author)
  •   Münch, Gerald (external author)
  •   Ooi, Lezanne

Publication Date


  • 2016

Citation


  • Balez, R., Steiner, N., Engel, M., Sanz Munoz, S., Lum, J. Stephen., Wu, Y., Wang, D., Vallotton, P., Sachdev, P., O'Connor, M., Sidhu, K., Münch, G. & Ooi, L. (2016). Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease. Scientific Reports, 6 31450-1-31450-11.

Scopus Eid


  • 2-s2.0-84982128208

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=5076&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/4052

Has Global Citation Frequency


Start Page


  • 31450-1

End Page


  • 31450-11

Volume


  • 6

Place Of Publication


  • United Kingdom

Abstract


  • Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, yet current

    therapeutic treatments are inadequate due to a complex disease pathogenesis. The plant polyphenol

    apigenin has been shown to have anti-inflammatory and neuroprotective properties in a number of

    cell and animal models; however a comprehensive assessment has not been performed in a human

    model of AD. Here we have used a human induced pluripotent stem cell (iPSC) model of familial and

    sporadic AD, in addition to healthy controls, to assess the neuroprotective activity of apigenin. The

    iPSC-derived AD neurons demonstrated a hyper-excitable calcium signalling phenotype, elevated levels

    of nitrite, increased cytotoxicity and apoptosis, reduced neurite length and increased susceptibility to

    inflammatory stress challenge from activated murine microglia, in comparison to control neurons. We

    identified that apigenin has potent anti-inflammatory properties with the ability to protect neurites

    and cell viability by promoting a global down-regulation of cytokine and nitric oxide (NO) release in

    inflammatory cells. In addition, we show that apigenin is able to protect iPSC-derived AD neurons

    via multiple means by reducing the frequency of spontaneous Ca2+ signals and significantly reducing

    caspase-3/7 mediated apoptosis. These data demonstrate the broad neuroprotective action of apigenin

    against AD pathogenesis in a human disease model.

Authors


  •   Balez, Rachelle (external author)
  •   Steiner, Nicole (external author)
  •   Engel, Martin
  •   Sanz Munoz, Sonia (external author)
  •   Lum, Jeremy
  •   Wu, Yizhen (external author)
  •   Wang, Dadong (external author)
  •   Vallotton, Pascal (external author)
  •   Sachdev, Perminder (external author)
  •   O'Connor, Michael D. (external author)
  •   Sidhu, Kuldip (external author)
  •   Münch, Gerald (external author)
  •   Ooi, Lezanne

Publication Date


  • 2016

Citation


  • Balez, R., Steiner, N., Engel, M., Sanz Munoz, S., Lum, J. Stephen., Wu, Y., Wang, D., Vallotton, P., Sachdev, P., O'Connor, M., Sidhu, K., Münch, G. & Ooi, L. (2016). Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease. Scientific Reports, 6 31450-1-31450-11.

Scopus Eid


  • 2-s2.0-84982128208

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=5076&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/4052

Has Global Citation Frequency


Start Page


  • 31450-1

End Page


  • 31450-11

Volume


  • 6

Place Of Publication


  • United Kingdom