Parkinson's disease (PD) is a common movement disorder marked by nigrostriatal dopaminergic neuronal loss that disturbs the communication in the basal ganglionic circuitry, and currently, no treatments are available for PD that could reverse this pathology (Bloem et al., 2021). In recent years, it has been shown that insulin desensitization can also occur in the brain, and an emerging body of evidence, including epidemiology, molecular genetics, and cell biology, has forged links between PD and type II diabetes mellitus (Fiory et al., 2019; Kim et al., 2017). Thus, correcting insulin signals in various ways has become a therapeutic strategy for PD. Incretin hormones are gut peptides that regulate islet function and blood glucose levels. In humans, the major incretin hormones are glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and together they fully account for the incretin effect (D. Sharma et al., 2018).

Although the physiological role of incretins in the brain is less known, the protective effects of novel GLP-1 analogs liraglutide or exendin-4 have been demonstrated to possess neuroprotective actions. It has been shown that exendin-4 has cellular and functional beneficial properties in improving neuronal transmission and protecting dopaminergic neurons in 6-hydroxydopamine (6-OHDA) (Bertilsson et al., 2008) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal models of PD (Li et al., 2009). Newer GLP-1 mimetics (liraglutide and lixisenatide), which are resistant to cleavage by DPP-IV, have much enhanced biological half-life in the blood and are reported to provide a better neuroprotective profile as compared with exendin-4 in MPTP-induced mouse model of PD (Liu et al., 2015). In addition, a dual GLP-1 and GIP receptor agonist has been reported to be neuroprotective and increase the brain-derived growth factor (BDNF) expression in experimental PD (Ji et al., 2016).

On the other hand, inhibition of DPP-IV is an effective way to increase incretin levels. Gliptins are oral anti-diabetic medications used to treat type II diabetes and its complications (Röhrborn et al., 2015). They raise incretin concentration by decreasing DPP-IV activity, raising glucagon and insulin release (Dunaevsky et al., 2020). It has been reported that gliptins reverse neurodegeneration in cell cultures and experimental animals. In addition, several DPP-IV inhibitors, like vildagliptin (Abdelsalam and Safar, 2015) and sitagliptin (Li et al., 2018), were previously verified for their anti-Parkinsonian effects. Alogliptin (Alo) is a particular and compelling DPP-IV inhibitor revealed to provide potential neuroprotective benefits in rats following brain ischemia/reperfusion (Yang et al., 2013) and decreased neuroinflammation in the hippocampi of diabetic rats (El-Sahar et al., 2021). Recently, Alo has been reported to abrogate rotenone-induced experimental PD in rats (Safar et al., 2021). In the current research, we have examined the protective effects of Alo in LPS-induced experimental PD in rats, with particular emphasis on motor functions, proinflammatory cytokines, and monoaminergic, glutamatergic, and GABAergic transmission.