MicroRNA‐190 alleviates neuronal damage and inhibits neuroinflammation via Nlrp3 in MPTP‐induced Parkinson's disease mouse model

Abstract

Parkinson's disease (PD) is neurodegenerative dyskinesia characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Although neuroinflammation is one of the pathological features of PD, its mechanism of promoting PD is still not fully understood. Recently, the microRNA (miR) is considered to play a critical regulatory role in inflammatory responses. In this study, we examined the antiinflammatory activity, antineuronal injury, and the underlying target of miR-190 with MPTP-induced PD mouse model and BV2 cells. The results showed that miR-190 is downregulated in lipopolysaccharide (LPS)-induced BV2 cells; however, when the miR-190 overexpressed, the expression of proinflammatory mediators, such as iNOS, IL-6, TNF-α, and TGF-β1, were inhibited and the anti-inflammatory mediator such IL-10 was increased.In addition, we predicted the potential target of miR-190 to be Nlrp3 and verified by luciferase reporter assay. The results also showed that Nlrp3 was upregulated in LPSinduced BV2 cells, whereas knockdown of Nlrp3 inhibited the LPS-induced inflammatory response in BV2 cells. Furthermore, upregulation of miR-190 or knockdown of Nlrp3 inhibited LPS-induced apoptosis in BV2 cells. However, the apoptosis inhibition effect of miR-190 was abrogated by overexpression of Nlrp3. Finally, upregulation of miR-190 inhibited the activation of microglial cells and inflammation and attenuated the tyrosine hydroxylase loss in SNpc in MPTP-induced PD mice. In conclusion, we demonstrated that miR-190 alleviates neuronal damage and inhibits inflammation via negatively regulating the expression and activation of Nlrp3 in MPTP-induced PD mouse model.

miR‐29c‐3p inhibits microglial NLRP3 inflammasome activation by targeting NFAT5 in Parkinson's disease

“…Our previous study showed that the decreased expression of miR‐29c suppressed the inflammation in MPP + ‐induced SH‐SY5Y neurons and MPTP‐treated animals (Wang, Yang, et al, 2019). The main features of PD are defined as microglial activation and dopaminergic neuron loss (Kong et al, 2019; Sun et al, 2019). In this study, we further found a significant reduction of miR‐29c in LPS‐induced BV‐2 cells, indicating its potential role in the regulation of microglial inflammation in PD.…”

“…NLRP3 inflammasome activation has been shown to participate in modulating the inflammation of microglia in PD (Chen et al, 2019; Sun et al, 2019). The NLRP3 inflammasome is a molecular complex that composed of NLRPS, ASC and caspase‐1, and its activation promoted IL‐1β production to induce inflammation (Yang et al, 2019).…”

Transcriptomic approach predicts a major role for transforming growth factor beta type 1 pathway in L‐Dopa‐induced dyskinesia in parkinsonian rats

“…We have also identified the ERK centered “neurological” gene network involving 35 upregulated genes associated with “function” of nervous system (Figure 4B). Notably, among the key LID‐associated genes identified in this study, CFLAR , CRYAB , GADD45A , GJB6 , TAC1 , TH , HSPA5 , HTR1B , NPTX2 are known to play a role in neuronal inflammation 31,33‐42 and TAC1 and TH are directly associated with PD 31 (Table S4). Therefore, gene networking analyses identified AKT and ERK centered gene networks in the striatum of L‐Dopa‐treated rats regulating key transcriptional programs.…”

Development of early diagnosis of Parkinson's disease: Illusion or reality?

“…19,75,80 Along with proteinopathies, neuroinflammation contributes to the progression of PD, which is associated with an increased level of toxic cytokines in CSF and plasma. 13,19,43,81,82 MicroRNAs, that control the expression of risk genes and are contained in CSF in free form and in exosomes, are also considered PD biomarkers. 16,83 The diagnostic sensitivity of the miRNAs panel reaches 90%.…”