Molecular Neurobiology

, Volume 54, Issue 6, pp 4292–4302 | Cite as

Caspase-1 Deficiency Alleviates Dopaminergic Neuronal Death via Inhibiting Caspase-7/AIF Pathway in MPTP/p Mouse Model of Parkinson’s Disease

  • Chen Qiao
  • Lin-Xia Zhang
  • Xi-Yang Sun
  • Jian-Hua Ding
  • Ming Lu
  • Gang Hu
Article

Abstract

Caspase family has been recognized to be involved in dopaminergic (DA) neuronal death and to exert an unfavorable role in Parkinson’s disease (PD) pathology. Our previous study has revealed that caspase-1, as an important component of NLRP3 inflammasome, induces microglia-mediated neuroinflammation in the pathogenesis of PD. However, the role of caspase-1 in DA neuronal degeneration in the onset of PD remains unclear. Here, we showed that caspase-1 knockout ameliorated DA neuronal loss and dyskinesia in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p)-induced PD model mice. We further found that caspase-1 knockout decreased MPTP/p-induced caspase-7 cleavage, subsequently inhibited nuclear translocation of poly (ADP-ribose) polymerase 1 (PARP1), and reduced the release of apoptosis-inducing factor (AIF). Consistently, we demonstrated that caspase-1 inhibitor suppressed caspase-7/PARP1/AIF-mediated apoptosis pathway by 1-methyl-4-phenylpyridinium ion (MPP+) stimulation in SH-SY5Y cells. Caspase-7 overexpression reduced the protective effects of caspase-1 inhibitor on SH-SY5Y cell apoptosis. Collectively, our results have revealed that caspase-1 regulates DA neuronal death in the pathogenesis of PD in mice via caspase-7/PARP1/AIF pathway. These findings will shed new insight into the potential of caspase-1 as a target for PD therapy.

Keywords

Caspase-1 Caspase-7 Poly (ADP-ribose) polymerase 1 Apoptosis-inducing factor Dopaminergic neuron Parkinson’s disease 

Supplementary material

12035_2016_9980_MOESM1_ESM.docx (305 kb)
ESM 1 (DOCX 305 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Chen Qiao
    • 1
  • Lin-Xia Zhang
    • 1
  • Xi-Yang Sun
    • 1
  • Jian-Hua Ding
    • 1
  • Ming Lu
    • 1
  • Gang Hu
    • 1
    • 2
  1. 1.Jiangsu Key Laboratory of Neurodegeneration, Department of PharmacologyNanjing Medical UniversityNanjingChina
  2. 2.Department of PharmacologyNanjing University of Chinese MedicineNanjingChina

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