title: The NLRP3 Inflammasome is Involved in the Pathogenesis of Parkinson's Disease in Rats.
abstract: The etiology and pathogenesis of Parkinson's disease (PD) are complicated and have not been fully elucidated, but an important association has been identified between inflammation and PD. In this study, we investigated the role of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing (NLRP) 3 inflammasome, consisting of NLRP3, caspase-1 and cytokines of the IL-1 family, in lipopolysaccharide (LPS)-induced and 6-hydroxydopamine (6-OHDA)-induced PD rats. Microinjection of different doses of caspase-1 inhibitor (Ac-YVAD-CMK, 300 or 1200 ng/rat) was performed for seven consecutive days. Then, rotational behavior, the number of dopamine (DA) neurons in the substantia nigra pars compacta (SNc), and the mRNA and protein expression levels of NLRP3 inflammasome components were measured 14 days after the microinjection setup was established. Results showed that high mRNA and protein expression levels of NLRP3 inflammasome components were observed in the injected side of the LPS- and 6-OHDA-induced PD rats; Ac-YVAD-CMK inhibited the mRNA and protein expression of NLRP3 inflammasome components in both LPS- and 6-OHDA-induced PD rats. Moreover, the number of rotations was significantly decreased, and the number of DA neurons in the SNc improved. Our data indicate that the NLRP3 inflammasome participates in the pathogenesis of PD and that inhibiting the downstream pathway of the NLRP3/caspase-1/IL-1β axis can alleviate the occurrence of PD symptoms, providing a new basis for the prevention and treatment of PD.
authors.affiliation: Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
authors.forename: Zhijuan
authors.initials: Z
authors.lastname: Mao
authors.affiliation: Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
authors.forename: Chanchan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
authors.forename: Suqiong
authors.initials: S
authors.lastname: Ji
authors.affiliation: Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
authors.forename: Qingmei
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Neurology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China. xuezheng@hotmail.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xue
mesh_terms: D000818:Animals; D058847:Inflammasomes / Q000096:biosynthesis*; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000096:biosynthesis*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D016627:Oxidopamine
keywords: 6-OHDA; Ac-YVAD-CMK; LPS; NLRP3 inflammasome; Parkinson’s disease