Upregulation of the PI3K/AKT and Nrf2 Pathways by the DPP-4 Inhibitor Sitagliptin Renders Neuroprotection in Chemically Induced Parkinson’s Disease Mouse Models DOI
Ritu Soni,

Vaishali Pankaj,

Sudeep Roy

и другие.

ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Parkinson's disease (PD) is one of the most common progressive neurodegenerative pathologies that leads to dopaminergic deficiency and motor manifestations. Alpha-synuclein aggregation a characteristic hallmark PD pathogenesis. These aggregates facilitate formation Lewy bodies degeneration. The epidemiological evidence demonstrates definitive association diabetes with risk. Considering this, many antidiabetic agents such as GLP-1 agonists DPP-4 inhibitors are being explored alternative therapeutics. This study evaluated neuroprotective effect inhibitor sitagliptin mediated by PI3K/AKT Nrf2 pathways in models. In silico studies were conducted determine binding affinity, stability, ADMET properties target proteins. Sitagliptin (15 mg/kg p.o.) was administered rotenone (30 p.o. for 28 days)-induced MPTP/P (25 i.p. MPTP 100 probenecid twice week 5 weeks)-induced mouse (C57/BL6) Neurobehavioral assessments carried out throughout study. Biochemical (GSH, MDA), molecular estimations (AKT, Nrf2, PI3K, GSK-3β, GLP1, CREB, BDNF, NF-κB, alpha-synuclein), histopathological studies, immunohistochemistry at end demonstrate better binding, profile both restored cognitive deficits rotenone- MPTP/P-induced There upregulation AKT, BDNF levels downregulation alpha-synuclein models after treatment sitagliptin. However, GLP1 not significantly restored, indicating GLP1-independent mechanism. It also alterations TH+ neuronal loss induced MPTP/P. findings exhibits action PD.

Язык: Английский

Upregulation of the PI3K/AKT and Nrf2 Pathways by the DPP-4 Inhibitor Sitagliptin Renders Neuroprotection in Chemically Induced Parkinson’s Disease Mouse Models DOI
Ritu Soni,

Vaishali Pankaj,

Sudeep Roy

и другие.

ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Parkinson's disease (PD) is one of the most common progressive neurodegenerative pathologies that leads to dopaminergic deficiency and motor manifestations. Alpha-synuclein aggregation a characteristic hallmark PD pathogenesis. These aggregates facilitate formation Lewy bodies degeneration. The epidemiological evidence demonstrates definitive association diabetes with risk. Considering this, many antidiabetic agents such as GLP-1 agonists DPP-4 inhibitors are being explored alternative therapeutics. This study evaluated neuroprotective effect inhibitor sitagliptin mediated by PI3K/AKT Nrf2 pathways in models. In silico studies were conducted determine binding affinity, stability, ADMET properties target proteins. Sitagliptin (15 mg/kg p.o.) was administered rotenone (30 p.o. for 28 days)-induced MPTP/P (25 i.p. MPTP 100 probenecid twice week 5 weeks)-induced mouse (C57/BL6) Neurobehavioral assessments carried out throughout study. Biochemical (GSH, MDA), molecular estimations (AKT, Nrf2, PI3K, GSK-3β, GLP1, CREB, BDNF, NF-κB, alpha-synuclein), histopathological studies, immunohistochemistry at end demonstrate better binding, profile both restored cognitive deficits rotenone- MPTP/P-induced There upregulation AKT, BDNF levels downregulation alpha-synuclein models after treatment sitagliptin. However, GLP1 not significantly restored, indicating GLP1-independent mechanism. It also alterations TH+ neuronal loss induced MPTP/P. findings exhibits action PD.

Язык: Английский

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