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GLP-1R activation of neuroprotective pathways in neurons, microglia and astrocytes has also been reported: improvements in overall cognition, learning and motor function potentially associated with GLP-1RA administration in Alzheimers disease and Parkinsons disease may be mediated not only by their amyloid pathology-ameliorating properties (A, tau and -synuclein), but also the suppression of Ca 2+ deregulation and endoplasmic reticulum stress, anti-inflammatory activity, blockage of oxidative stress, mitochondrial dysfunction and apoptosis pathways, enhancements in the neuronal insulin sensitivity and energy metabolism, functional improvements in autophagy and mitophagy, elevated brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor synthesis, and neurogenesis 36

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doi: 10.1038/s41598-019-38956-2 94 WickiAWildDStorchDSeemayerCGotthardtMBeheMet al