Objective: To elucidate the role of NLRP3 Inflammasome in PD pathogenesis and its role in differential susceptibility.
Background: Inflammasomes play a role in the progression of neurodegenerative diseases like PD. Given the less invasive nature of blood-based investigations, this study aimed to measure the levels of NLRP3-associated cytokines in the serum of PD patients. Additionally, the study aimed to target NLRP3 pathway using small molecule PD180970 in MPTP-susceptible (C57BL/6) and MPTP-resistant (CD-1) mice to determine the role of susceptibility.
Method: PD patients, diagnosed by neurologists (Movement Disorder Specialists) were recruited from the Dept. of Neurology, NIMHANS. The study included: 48 PD patients (equal no. of male and female) and 32-matched controls. Blood samples were collected and serum levels were analysed using ELISA. Mice (n=4/strain/condition; 15-17 w) received either saline or MPTP (15 mg/kg, i.p.,4 doses at 2-hr intervals). PD180970(5 mg/kg,i.p.) was administered from D4 post-MPTP for 7 days, and motor function was assessed using Pole test and serum was isolated at terminal experiment.
Results: PD patients had significantly higher levels of NLRP3, Caspase-1, IL-18, IL-33, and IL-1β (Control vs PD; p<0.0001), compared to controls. NLRP3 showed strong correlation with Caspase-1 (p=0.05). Similarly, C57BL/6J MPTP mice showed significantly higher NLRP3 levels compared to CD-1(C57BL/6Jvs CD-1; ****p<0.0001). PD180970 effected partial reduction of levels in C57BL/6J vis-à-vis a complete reversal in CD-1. In the pole test, the time taken to T-turn and time to descend were significantly higher in C57BL/6J MPTP (control vs. MPTP; ****p<0.0001) whereas in CD-1 they remained comparable. PD180970 facilitated complete motor recovery of only MPTP-injected CD-1 (Control vs. MPTP+PD180970; ***p<0.001).
Conclusion: NLRP3-associated cytokines are potential blood-based biomarkers and therapeutic targets in PD.The correlation between NLRP3 and Caspase-1 hints at a prospect of formation of NLRP3-ASC-Caspase-1 complex; which could be a target to halt the disease, confirmed through our in vivo findings. Albeit its efficacy varies based on the inherent susceptibility, emphasizing the need for personalized treatment approaches in PD.
To cite this abstract in AMA style:
S. Choudhury, N. Kamble, V. Holla, S. M, P. Pal, R. Yadav, P. Alladi. Investigating the role of NLRP3 Inflammasome as Biomarkers and Therapeutic Targets in Parkinson’s Disease Pathogenesis [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/investigating-the-role-of-nlrp3-inflammasome-as-biomarkers-and-therapeutic-targets-in-parkinsons-disease-pathogenesis/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/investigating-the-role-of-nlrp3-inflammasome-as-biomarkers-and-therapeutic-targets-in-parkinsons-disease-pathogenesis/