Abstract
The NLR family pyrin domain containing 3 (NLRP3) inflammasome was reported to be regulated by autophagy and activated during inflammatory procession of Parkinson’s disease (PD). Berberine (BBR) is well-studied to play an important role in promoting anti-inflammatory response to mediate the autophagy activity. However, the effect of Berberine on NLRP3 inflammasome in PD and its potential mechanisms remain unclear. Hence, in this study, we investigated the effects of BBR on 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, by evaluating their behavioral changes, dopaminergic (DA) neurons loss, neuroinflammation, NLRP3 inflammasome and autophagic activity. BBR was also applied in BV2 cells treated with 1-methyl-4-pehnyl-pyridine (MPP+). The autophagy inhibitor 3-Methyladenine (3-MA) was administrated to block autophagy activity both in vivo and in vitro. In our in vivo studies, compared to MPTP group, mice in MPTP + BBR group showed significant amelioration of behavioral disorders, mitigation of neurotoxicity and NLRP3-associated neuroinflammation, enhancement of the autophagic process in substantia nigra (SN). In vitro, compared to MPP+ group, BBR significantly decreased the level of NLRP3 inflammasome including the expressions of NLRP3, PYD and CARD domain containing (PYCARD), cleaved caspase 1 (CASP1), and mature interleukin 1 beta (IL1B), via enhancing autophagic activity. Furthermore, BBR treatment increased the formation of autophagosomes in MPP+-treated BV2 cells. Taken together, our data indicated that BBR prevents NLRP3 inflammasome activation and restores autophagic activity to protect DA neurons against degeneration in vivo and in vitro, suggesting that BBR may be a potential therapeutic to treat PD.
Highlights
Parkinson’s disease (PD) is characterized by loss of dopaminergic (DA) neurons and formation of Lewy bodies in substantia nigra (SN), afflicting approximately 1% of the population aged 60 years and older worldwide (Ascherio and Schwarzschild, 2016)
Compared to the control group, mice in the other four groups all showed no significant difference in body weight at all time points (p > 0.05, Figure 1E)
We found that MPTP induced the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome in microglia which led to DA neuron degeneration and behavior dysfunction in mice
Summary
Parkinson’s disease (PD) is characterized by loss of dopaminergic (DA) neurons and formation of Lewy bodies in substantia nigra (SN), afflicting approximately 1% of the population aged 60 years and older worldwide (Ascherio and Schwarzschild, 2016). Numerous studies have demonstrated that NLR family pyrin domain containing 3 (NLRP3) inflammasome plays a vital role in the pathogenesis of PD (Haque et al, 2020). The activation of NLRP3 inflammasome triggered by toxins leads to the cleavage of caspase 1 (CASP1) into cleaved CASP1, which results in the secretion of interleukin 1 beta (IL1B) and interleukin 18 (IL18) to induce neuroinflammation and neuron death (Heneka et al, 2018). NLRP3 inflammasome accumulates in microglia of 1methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced mice and leads to DA neurons loss (Lee et al, 2019). Recent studies have reported that MPP+ can activate NLRP3 inflammasome in microglia (Yao et al, 2019; Zeng et al, 2019; Cheng et al, 2020). Inhibition of NLRP3 inflammasome activation may be a critical strategy to alleviate PD neuroinflammation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
