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Table 1 RyR-mediated calcium deregulation in AD

From: Ryanodine receptors: physiological function and deregulation in Alzheimer disease

AD models Study systems RyR-mediated [Ca2+] dysregulations References
PS1M146V and PS1L250S SH-SY5Y cells Dantrolene blocked ↑ carbachol-induced [Ca2+] signals (vs. wild type PS1) [93]
3xTgAD mice PS1M146V KI Tg mice Primary cortical neurons ↑ caffeine-induced [Ca2+] signals (vs. wt neurons) [94]
PS1WT, PS1L286V, PS1 M146V, PS2 N141L PC12 cells ↑ caffeine-induced [Ca2+] signals (vs. vector transfected cells) [95, 96]
APPwt and APPswe SH-SY5Y cells ↑ caffeine-induced [Ca2+] signals (vs. vector transfected cells) [92]
Tg2576 mice hippocampal primary neurons ↑ caffeine-induced [Ca2+] signals (vs. wt neurons) [92]
PS M146V KI Tg and 3xTgAD mice Acute brain slice preparation (6w, 6 mo and 1.5 Y) (*) ↑ caffeine-induced [Ca2+] signals [72, 100]
Dantrolene reduced the IP3-evoked Ca2+ responses (vs. wt-derived brain slices)
Extracellular Aβ42 application Primary Cortical neurons siRyR-3 blocked increased ryanodine- and glutamate-induced [Ca2+] signals upon Aβ42 application (vs. Aβ42 non-treated neurons) [91]
PScDKO Tg and 3xTgAD mice Primary hippocampal neurons ↑ caffeine-induced [Ca2+] signals (vs. wt-Tg neurons) [78]
↑ ER Ca2+ pool (vs. wt-Tg neurons)
PScDKO Tg mice Primary hippocampal neurons ↔ ER Ca2+ pool [97]
↓ caffeine-induced [Ca2+] signals (vs. wt neurons)
PS2N141L Tg and PS2N141L/APPswe mice Primary neuronal cultures and acute brain slice preparation ↓ ER [Ca2+] [101]
↓ IP3-generating Ca2+ responses
↑ caffeine-induced [Ca2+] signals (vs. wt-Tg neurons)
PS1M146VKI Tg and PS1M146V/APPswe Tg mice Acute brain slice preparation ↑ caffeine-induced [Ca2+] signals [102]
RyR blockade prevents NMDA Ca2+ response (vs. wt-derived brain slices)
  1. Abbreviations: [Ca2+] calcium signals are depicted as ↑ (increased), ↓ (reduced), or ↔ (unchanged) as compared to respective controls, (*) study was performed on acute brain slice preparation isolated from transgenic mice at different ages (6 weeks (w), 6 months (mo) and 1.5 years (Y), vs versus, KI knock in, Tg Transgenic, wt Wild type, PScKO Tg mice are conditionally double knock out for PS1 and PS2, Tg2576 mice express the βAPP harboring Swedish double mutation (APP K670N / M671L ), 3xTgAD mice are generated from the PS1M146V KI mouse overexpressing APPswe and TauP130L.