NLRP3 Inflammasome-Mediated Neuroinflammation and Related Mitochondrial Impairment in Parkinson's Disease / 神经科学通报·英文版

Parkinson's disease (PD) is a common neurodegenerative disorder caused by the loss of dopamine neurons in the substantia nigra and the formation of Lewy bodies, which are mainly composed of alpha-synuclein fibrils. Alpha-synuclein plays a vital role in the neuroinflammation mediated by the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in PD. A better understanding of the NLRP3 inflammasome-mediated neuroinflammation and the related mitochondrial impairment during PD progression may facilitate the development of promising therapies for PD. This review focuses on the molecular mechanisms underlying NLRP3 inflammasome activation, comprising priming and protein complex assembly, as well as the role of mitochondrial impairment and its subsequent inflammatory effects on the progression of neurodegeneration in PD. In addition, the therapeutic strategies targeting the NLRP3 inflammasome for PD treatment are discussed, including the inhibitors of NLRP3 inflammatory pathways, mitochondria-focused treatments, microRNAs, and other therapeutic compounds.

Detection of intestinal microbial changes in rotenone-induced Parkinson' s disease model mice / 解剖学报

[Abstract] Objective To investigate the changes of intestinal microbes in rotenone-induced Parkinson' s disease (PD) mice based on 16S rRNA gene sequencing. Methods Fourteen 8-week-old male C57BL/6J mice were randomly divided into two groups: 6 mice in the control group and 8 mice in the model group. The model mice were injected subcutaneously with rotenone (3 mg/kg) for 5 weeks, and the bod)' weight was measured once a week. After 5 weeks, behavioral tests were perfonned, including the rotating rod test and the open field test. The contents of the tract were used for intestinal microbial detection analysis. Results After 5 weeks of rotenone treatment, the weight of PD mice was significantly lower than that of the control mice(P 0. 05), but the microbial species showed significant differences. Among them, the PD mice showed a significant decrease in the intestinal Turicibacter (P < 0 . 0 1), a significant increase in norank f Lachnospiraceae (P < 0. 01), a significant decrease in norank_f Erysipelotrichaceae(P<0. 01), and a significant increase in Lachnoclostridium{ P<0. 0 1) . Conclusion Intestinal microbes in PD mice are disordered, and these intestinal flora ma)' be involved in the development of dyskinesia in PD mice.