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Model-based incremental effects are summarized in Table 2

Abbreviations GLP-1RAs: Glucagon-like peptide-1 receptor agonists T2DM: Type 2 diabetes mellitus DPP-4: Dipeptidyl peptidase IV GLP-1R: Glucagon-like peptide-1 receptor cAMP: Cyclic adenosine monophosphate PKA: Protein kinase A PI3K: Phosphatidylinositol 3-kinase Akt: Protein kinase B AD: Alzheimers diseases TRPV1: Transient receptor potential vanilloid 1 OA: Osteoarthritis KOA: Knee OA MIA: Monoiodoacetate IL-6: Interleukin 6 PGE2: Prostaglandin E2 NO: Nitric oxide ER: Endoplasmic reticulum IL-1: Interleukin-1 MMP-3: Matrix metalloproteinases-3 MMP-13: Matrix metalloproteinases-13 ROS: Reactive oxygen species BMI: Body mass index IBS: Irritable bowel syndrome ATP: Adenosine triphosphate SERT: Serotonin transporter TPH-1: Tryptophan hydroxylase-1 AC: Adenylate cyclase LPS: Lipopolysaccharide WAS: Water avoidance stress IBS-C: Constipation-predominant IBS SNL: Spinal nerve ligation SCI: Spinal cord injury CHOP: C/EBP homologous transcription factor protein GRP78: Glucose regulatory protein 78 PSNT: Partial sciatic nerve transection L

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Mounting evidence suggests that the impairment of mitochondrial respiratory chain, in particular complex I deficiency and the subsequent increase in ROS production may directly or indirectly contribute to the pathology of sporadic PD 23,24