The mechanism behind activation of the Nod-like receptor family protein 3 inflammasome in Parkinson's disease

Previous studies have shown that the ATP-P2X4 receptor signaling pathway mediates the activation of the Nod-like receptor family protein 3 (NLRP3) inflammasome. The NLRP3 inflammasome may promote renal interstitial inflammation in diabetic nephropathy. As inflammation also plays an important role in...

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Bibliographic Details
Published in:Neural regeneration research 2022-04, Vol.17 (4), p.898-904
Main Authors: Wang, Jing, Zhang, Xiao-Na, Fang, Jin-Ni, Hua, Fei-Fei, Han, Jing-Yang, Yuan, Zeng-Qiang, Xie, An-Mu
Format: Article
Language:English
Subjects:
atp
neurodegenerative disorder
neuroinflammation
neuroinflammatory response
nlrp3
p2x4
parkinson’s disease
Cytokines
Diabetic nephropathy
Neurodegeneration
Parkinson's disease
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Summary:Previous studies have shown that the ATP-P2X4 receptor signaling pathway mediates the activation of the Nod-like receptor family protein 3 (NLRP3) inflammasome. The NLRP3 inflammasome may promote renal interstitial inflammation in diabetic nephropathy. As inflammation also plays an important role in the pathogenesis of Parkinson's disease, we hypothesized that the ATP-P2X4 receptor signaling pathway may activate the NLRP3 inflammasome in Parkinson's disease. A male rat model of Parkinson's disease was induced by stereotactic injection of 6-hydroxydopamine into the pars compacta of the substantia nigra. The P2X4 receptor and the NLRP3 inflammasome (interleukin-1β and interleukin-18) were activated. Intracerebroventricular injection of the selective P2X4 receptor antagonist 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD) or knockdown of P2X4 receptor expression by siRNA inhibited the activation of the NLRP3 inflammasome and alleviated dopaminergic neurodegeneration and neuroinflammation. Our results suggest that the ATP-P2X4 receptor signaling pathway mediates NLRP3 inflammasome activation, dopaminergic neurodegeneration, and dopamine levels. These findings reveal a novel role of the ATP-P2X4 axis in the molecular mechanisms underlying Parkinson's disease, thus providing a new target for treatment. This study was approved by the Animal Ethics Committee of Qingdao University, China, on March 5, 2015 (approval No. QYFYWZLL 26119).
ISSN:1673-5374
1876-7958
DOI:10.4103/1673-5374.323077