The effect of citalopram treatment on amyloid-β precursor protein processing and oxidative stress in human hNSC-derived neurons

R. J. Elsworthy, J. A. Crowe, M. C. King, C. Dunleavy, E. Fisher, A. Ludlam, H. R. Parri, E. J. Hill, S. Aldred

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Selective Serotonin Reuptake Inhibitors (SSRIs) may hold therapeutic benefits for people with Alzheimer’s disease (AD). SSRIs may perturb AD progression, or the conversion from MCI to AD, via increased neurogenesis, reduced oxidative stress and/or favourable Amyloid-β Precursor Protein (AβPP) processing. This study used iPSC derived cortical neuronal cells carrying 3 different PSEN1 mutations, to investigate the effect of treatment with the SSRI, Citalopram on AβPP processing and oxidative stress. Control and PSEN1 mutation (L286V, A246E, M146L) iPSC-derived neurons were treated with Citalopram for 45 days. ADAM10 activity, AβPP processing and Aβ generation was measured in addition to cellular redox status. Citalopram treatment reduced the Aβ1-42:40 ratio in control but not in fAD PSEN1 cells. ADAM10 activity was increased with Citalopram treatments in fAD PSEN1 cell lines, which was also seen for sAβPPα secretion. Lower superoxide generation in fAD PSEN1 cells following Citalopram treatment was identified, although there was no effect on end markers of oxidative stress. Treatment with Citalopram appears to have little effect on Aβ generation in fADPSEN1 cells, but our findings suggest that treatment can significantly increase non-amyloidogenic AβPP processing and reduce oxidative stress. These changes may explain why SSRIs appear most effective in the prodromal period of the disease progression, as opposed to reducing established AD pathology. Further investigation of specific pathways conferring the beneficial effects of SSRIs treatment are warranted.

Originalspråkengelska
Artikelnummer285
TidskriftTranslational Psychiatry
Volym12
Nummer1
DOI
StatusPublished - 2022 dec.

Ämnesklassifikation (UKÄ)

  • Neurovetenskaper

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