Home > Research > Publications & Outputs > Liraglutide restores chronic ER stress, autopha...

Electronic data

Links

Text available via DOI:

View graph of relations

Liraglutide restores chronic ER stress, autophagy impairments and apoptotic signalling in SH-SY5Y cells

Research output: Contribution to journalJournal article

Published

Standard

Liraglutide restores chronic ER stress, autophagy impairments and apoptotic signalling in SH-SY5Y cells. / Panagaki, Theodora; Michael, Maria; Hölscher, Christian.

In: Scientific Reports, Vol. 7, 16158, 23.11.2017.

Research output: Contribution to journalJournal article

Harvard

APA

Vancouver

Author

Bibtex

@article{2aeeb223fbf04e0a9cb4e208370c523f,
title = "Liraglutide restores chronic ER stress, autophagy impairments and apoptotic signalling in SH-SY5Y cells",
abstract = "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.",
author = "Theodora Panagaki and Maria Michael and Christian H{\"o}lscher",
year = "2017",
month = "11",
day = "23",
doi = "10.1038/s41598-017-16488-x",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

RIS

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 -