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While these outcomes are based on large clinical trials (STEP 1 and SURMOUNT-1), weight loss should still be approached with realistic expectations, personalized goals, and ongoing support

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It has been reported that GLP-1 RA reduces tau phosphorylation through Akt and GSK-3, a pathway related to insulin signaling, which also confirmed that insulin resistance is the key to tau phosphorylation.186188 It has also been reported that the effects of liraglutide on decreasing the hyperphosphorylation of tau by enhancing O-glycosylation of neuronal cytoskeleton protein, improving the JNK and ERK signaling pathway.189,190 In addition, the mitochondrial PGC-1 signaling pathway is also the mechanism of GLP-1 RA to protect neurons from tau hyperphosphorylation, indicating that mitochondrial dysregulation has crosstalk with tau pathology.46 The common mechanism of GLP-1 RA reduction in A overproduction and tau hyperphosphorylation may be the restoration of protein phosphatase 2A activity and inhibition of - and - secretase.191 The mechanism of GLP-1 RA to improve dopaminergic degeneration and pathological -synuclein aggregation in the PD model may involve inhibiting the PI3K/Akt/mTOR pathway192 and enhancing AMPK/PGC-1a signaling pathway.193 Although some results have been achieved in animal models, clinical studies on GLP-1 RA remain limited

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