Final published version, 4.78 MB, PDF document
Available under license: CC BY: Creative Commons Attribution 4.0 International License
Final published version
Licence: CC BY: Creative Commons Attribution 4.0 International License
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Liraglutide restores chronic ER stress, autophagy impairments and apoptotic signalling in SH-SY5Y cells
AU - Panagaki, Theodora
AU - Michael, Maria
AU - Hölscher, Christian
PY - 2017/11/23
Y1 - 2017/11/23
N2 - Growing evidence suggests that agonists of glucagon-like peptide (GLP-1) receptor exert neuroprotective and neurorestorative effects across a range of experimental models of neuronal degeneration, and, recently, a pilot clinical trial of Liraglutide in Alzheimer's disease patients showed improvements in cerebral glucose consumption that signifies disease progression. However, the exact underlying mechanism of action remains unclear. Chronic endoplasmic reticulum (ER) stress has recently emerged as a mechanism for neuronal injury, rendering it a potent therapeutic target for acute and chronic neurodegenerative disorders. Here, we investigate the neuroprotective effects of Liraglutide along with the signalling network against prolong ER stress and autophagy impairments induced by the non-competitive inhibitor of sarco/ER Ca2+-ATPase, thapsigargin. We show that Liraglutide modulates the ER stress response and elicits ER proteostasis and autophagy machinery homeostasis in human SH-SY5Y neuroblastoma cell line. These effects correlate with resolution of hyper-activity of the antioxidant Nrf2 factor and restoration of the impaired cell viability and proliferation. Mechanistically, Liraglutide engages Akt and signal transducer and activator of transcription 3 (STAT3) signalling to favour adaptive responses and shift cell fate from apoptosis to survival under chronic stress conditions in SH-SY5Y cells.
AB - Growing evidence suggests that agonists of glucagon-like peptide (GLP-1) receptor exert neuroprotective and neurorestorative effects across a range of experimental models of neuronal degeneration, and, recently, a pilot clinical trial of Liraglutide in Alzheimer's disease patients showed improvements in cerebral glucose consumption that signifies disease progression. However, the exact underlying mechanism of action remains unclear. Chronic endoplasmic reticulum (ER) stress has recently emerged as a mechanism for neuronal injury, rendering it a potent therapeutic target for acute and chronic neurodegenerative disorders. Here, we investigate the neuroprotective effects of Liraglutide along with the signalling network against prolong ER stress and autophagy impairments induced by the non-competitive inhibitor of sarco/ER Ca2+-ATPase, thapsigargin. We show that Liraglutide modulates the ER stress response and elicits ER proteostasis and autophagy machinery homeostasis in human SH-SY5Y neuroblastoma cell line. These effects correlate with resolution of hyper-activity of the antioxidant Nrf2 factor and restoration of the impaired cell viability and proliferation. Mechanistically, Liraglutide engages Akt and signal transducer and activator of transcription 3 (STAT3) signalling to favour adaptive responses and shift cell fate from apoptosis to survival under chronic stress conditions in SH-SY5Y cells.
U2 - 10.1038/s41598-017-16488-x
DO - 10.1038/s41598-017-16488-x
M3 - Journal article
C2 - 29170452
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 16158
ER -