Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.22.36 (
caspase-1
)
6,285
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Caspase-1 Deficiency Alleviates Dopaminergic Neuronal Death via Inhibiting Caspase-7/AIF Pathway in MPTP/p Mouse Model of Parkinson's Disease. 2733 79
