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Familial Alzheimer’s disease presenilin-2 mutants affect Ca2+ homeostasis and brain network excitability

  • Diana Pendin
  • Cristina Fasolato
  • Emy Basso
  • Riccardo Filadi
  • Elisa Greotti
  • Luisa Galla
  • Chiara Gomiero
  • Alessandro Leparulo
  • Nelly Redolfi
  • Elena Scremin
  • Nicola Vajente
  • Tullio PozzanEmail author
  • Paola Pizzo
Short Communication
  • 34 Downloads

Abstract

Alzheimer’s disease (AD) is the most frequent cause of dementia in the elderly. Few cases are familial (FAD), due to autosomal dominant mutations in presenilin-1 (PS1), presenilin-2 (PS2) or amyloid precursor protein (APP). The three proteins are involved in the generation of amyloid-beta (Aβ) peptides, providing genetic support to the hypothesis of Aβ pathogenicity. However, clinical trials focused on the Aβ pathway failed in their attempt to modify disease progression, suggesting the existence of additional pathogenic mechanisms. Ca2+ dysregulation is a feature of cerebral aging, with an increased frequency and anticipated age of onset in several forms of neurodegeneration, including AD. Interestingly, FAD-linked PS1 and PS2 mutants alter multiple key cellular pathways, including Ca2+ signaling. By generating novel tools for measuring Ca2+ in living cells, and combining different approaches, we showed that FAD-linked PS2 mutants significantly alter cell Ca2+ signaling and brain network activity, as summarized below.

Keywords

Alzheimer’s disease Presenilin Calcium homeostasis Amyloid-beta Brain network Ca2+ probes 

Notes

Acknowledgments

This work was supported by the National Research Council of Italy (CNR), Research Project “Aging: molecular and technological innovations for improving the health of the elderly population” (Prot. MIUR 2867 25.11.2011). PS2.30H and B6.152H mouse lines were kindly donated by L. Ozmen and F. Hoffmann-La Roche Ltd. (Basel, Switzerland).

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Statement of human and animal rights

All procedures performed in the original studies described in this contribution were in accordance with the ethical standards of the institutional research committee (Ethical approval by the Ethical Committee of both the University of Padova and the Italian Ministry of Education, University and Research).

Informed consent

No human participants were included in the studies described in this contribution.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Diana Pendin
    • 1
    • 2
  • Cristina Fasolato
    • 2
  • Emy Basso
    • 1
    • 2
  • Riccardo Filadi
    • 1
    • 2
  • Elisa Greotti
    • 1
    • 2
  • Luisa Galla
    • 1
    • 2
  • Chiara Gomiero
    • 1
    • 2
  • Alessandro Leparulo
    • 2
  • Nelly Redolfi
    • 2
  • Elena Scremin
    • 2
  • Nicola Vajente
    • 2
  • Tullio Pozzan
    • 1
    • 2
    Email author
  • Paola Pizzo
    • 1
    • 2
  1. 1.Neuroscience Institute - Italian National Research Council (CNR)PaduaItaly
  2. 2.Department of Biomedical SciencesUniversity of PaduaPaduaItaly

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