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Liraglutide and its Neuroprotective Properties—Focus on Possible Biochemical Mechanisms in Alzheimer’s Disease and Cerebral Ischemic Events

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Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland
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Department of Obstetrics, Gynecology and Gynecological Oncology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Ujejskiego 75; 85-168 Bydgoszcz, Poland
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Department of Hepatobiliary and General Surgery. Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland
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Department of Pathophysiology of Hearing and Balance System, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(5), 1050; https://doi.org/10.3390/ijms20051050
Received: 15 February 2019 / Revised: 24 February 2019 / Accepted: 25 February 2019 / Published: 28 February 2019
(This article belongs to the Special Issue Kinase Signal Transduction 2019)
Liraglutide is a GLP-1 analog (glucagon like peptide-1) used primarily in the treatment of diabetes mellitus type 2 (DM2) and obesity. The literature starts to suggest that liraglutide may reduce the effects of ischemic stroke by activating anti-apoptotic pathways, as well as limiting the harmful effects of free radicals. The GLP-1R expression has been reported in the cerebral cortex, especially occipital and frontal lobes, the hypothalamus, and the thalamus. Liraglutide reduced the area of ischemia caused by MCAO (middle cerebral artery occlusion), limited neurological deficits, decreased hyperglycemia caused by stress, and presented anti-apoptotic effects by increasing the expression of Bcl-2 and Bcl-xl proteins and reduction of Bax and Bad protein expression. The pharmaceutical managed to decrease concentrations of proapoptotic factors, such as NF-κB (Nuclear Factor-kappa β), ICAM-1 (Intercellular Adhesion Molecule 1), caspase-3, and reduced the level of TUNEL-positive cells. Liraglutide was able to reduce the level of free radicals by decreasing the level of malondialdehyde (MDA), and increasing the superoxide dismutase level (SOD), glutathione (GSH), and catalase. Liraglutide may affect the neurovascular unit causing its remodeling, which seems to be crucial for recovery after stroke. Liraglutide may stabilize atherosclerotic plaque, as well as counteract its early formation and further development. Liraglutide, through its binding to GLP-1R (glucagon like peptide-1 receptor) and consequent activation of PI3K/MAPK (Phosphoinositide 3-kinase/mitogen associated protein kinase) dependent pathways, may have a positive impact on Aβ (amyloid beta) trafficking and clearance by increasing the presence of Aβ transporters in cerebrospinal fluid. Liraglutide seems to affect tau pathology. It is possible that liraglutide may have some stem cell stimulating properties. The effects may be connected with PKA (phosphorylase kinase A) activation. This paper presents potential mechanisms of liraglutide activity in conditions connected with neuronal damage, with special emphasis on Alzheimer’s disease and cerebral ischemia. View Full-Text
Keywords: liraglutide; neuroprotection; pathways; inflammation; Alzheimer’s disease; stroke liraglutide; neuroprotection; pathways; inflammation; Alzheimer’s disease; stroke
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Wiciński, M.; Socha, M.; Malinowski, B.; Wódkiewicz, E.; Walczak, M.; Górski, K.; Słupski, M.; Pawlak-Osińska, K. Liraglutide and its Neuroprotective Properties—Focus on Possible Biochemical Mechanisms in Alzheimer’s Disease and Cerebral Ischemic Events. Int. J. Mol. Sci. 2019, 20, 1050.

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