Scholarlink

<p>This study investigates the neuroprotective potential of the dipeptidyl peptidase-4 (DPP-4) inhibitors sitagliptin and vildagliptin in models of Parkinson’s disease (PD). In vitro, sitagliptin (10–80 µM) and vildagliptin (5–40 µM) enhanced mitophagy and modulated autophagy pathway in neuronal cell lines. Sitagliptin (20–80 µM) similarly promoted autophagy in <i>Drosophila</i> larval fat body. In an MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine)-induced mouse model of PD, administration of vildagliptin (15&#xa0;mg/kg/day) mitigated neuronal loss, reduced microglial activation, and increased tyrosine hydroxylase–positive neurons in the substantia nigra pars compacta and striatum. Network pharmacology and molecular docking analyses identified ten key protein targets, with DPP-4, serine/threonine-protein kinase AKT (AKT1) and glycogen synthase kinase-3 beta (GSK3β) emerging as central nodes. These findings indicate that both drugs engage a multi-target network to modulate autophagy and mitophagy, potentially facilitating the clearance of pathogenic protein aggregates and dysfunctional mitochondria. Together, these results position sitagliptin and vildagliptin as promising autophagy-modifying candidates for disease-modifying PD therapy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Neuroprotective effects of DPP-4 inhibitors sitagliptin and vildagliptin in Parkinson’s disease via autophagy modulation

  • 期刊论文

  • 发表日期：

    2026年3月16日

查看全文
  • Maiwulanijiang Yizibula,
  • Yimuranjiang Subuhati,
  • Adili Abudourousuli,
  • Xieraili Tuerxun,
  • Futao Chan,
  • Hengzhi Zhang,
  • Ainiwaer Wumaier,
  • Chimengul Turghun,
  • Mutalifu Aimaiti

摘要

This study investigates the neuroprotective potential of the dipeptidyl peptidase-4 (DPP-4) inhibitors sitagliptin and vildagliptin in models of Parkinson’s disease (PD). In vitro, sitagliptin (10–80 µM) and vildagliptin (5–40 µM) enhanced mitophagy and modulated autophagy pathway in neuronal cell lines. Sitagliptin (20–80 µM) similarly promoted autophagy in Drosophila larval fat body. In an MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine)-induced mouse model of PD, administration of vildagliptin (15 mg/kg/day) mitigated neuronal loss, reduced microglial activation, and increased tyrosine hydroxylase–positive neurons in the substantia nigra pars compacta and striatum. Network pharmacology and molecular docking analyses identified ten key protein targets, with DPP-4, serine/threonine-protein kinase AKT (AKT1) and glycogen synthase kinase-3 beta (GSK3β) emerging as central nodes. These findings indicate that both drugs engage a multi-target network to modulate autophagy and mitophagy, potentially facilitating the clearance of pathogenic protein aggregates and dysfunctional mitochondria. Together, these results position sitagliptin and vildagliptin as promising autophagy-modifying candidates for disease-modifying PD therapy.