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PHLPP1 deficiency alleviates dopaminergic neurodegeneration and represses neuroinflammation in Parkinson's disease

文献类型：期刊论文

作者Chen, Zhilin3,4; Liu, Yuan5; Zhao, Jinyue5; Zhou, Xin5; Han, Yudi3; Zhou, Zikai2; Liang, Huazheng1; Bi, Yong3,5
刊名BEHAVIORAL AND BRAIN FUNCTIONS
出版日期2025-09-29
卷号21期号:1页码:12
关键词Pleckstrin homology domain leucine-rich repeat protein phosphatases (PHLPP) Parkinson's disease Neuroinflammation NLRP3 Caspase1, IL-1 beta Proinflammatory cytokines Anti-inflammatory cytokines
DOI10.1186/s12993-025-00293-y
通讯作者Bi, Yong(drbiyong@126.com)
英文摘要BackgroundPleckstrin homology (PH) domain leucine-rich repeat protein phosphatases (PHLPP) has been associated with several neurodegenerative diseases, however, few studies have investigated the role of PHLPP in Parkinson's disease (PD). The present study aimed to answer this question through establishing a Parkinson's disease (PD) model using the Phlpp1-/- and wild-type (WT) mice and testing their behavioral as well as molecular changes. Methods: MPTP was intraperitoneal injected into mice to generate a PD model. Neurobehavioral parameters, protein expression and inflammatory cytokines release were measured by the open filed test, the pole test, immunohistochemistry, immunoblotting, immunoprecipitation, and quantitative reverse transcription PCR.ResultsMPTP-induced neurobehavioral deficits were more significantly ameliorated in PHLPP-KO-MPTP mice compared to WT-MPTP mice. The survival rate of TH+ neurons in the PHLPP-KO-MPTP group was higher than that in the WT-MPTP group (66% vs. 38%). Additionally, PHLPP1 knockout in KO-MPTP mice markedly reduced levels of IL-1 beta, IL-6, TNF-alpha, and iNOS, and increased levels of TGF-beta compared to those of WT-MPTP mice. Furthermore, PHLPP1 was found to bind to NLRP3 and that PHLPP1 knockout inhibited MPTP-induced expression of IL-1 beta and caspase-1 in substantia nigra of PD model mice.ConclusionOur results demonstrates that PHLPP1 knockout in PD model is positively associated with the survival of TH + neurons by suppressing inflammatory response in substantia nigra, suggesting that PHLPP1 plays a critical role in the development of PD.
WOS关键词REPEAT PROTEIN PHOSPHATASE ; MPTP MOUSE MODEL ; ALZHEIMERS-DISEASE ; ACTIVATION ; BRAIN ; INFLAMMATION ; CONTRIBUTES ; INHIBITION ; EXPRESSION ; MICROGLIA
资助项目National Natural Science Foundation of China
WOS研究方向Behavioral Sciences ; Neurosciences & Neurology
语种英语
WOS记录号WOS:001586095000001
出版者BMC
源URL[http://119.78.100.183/handle/2S10ELR8/321630]  
专题中国科学院上海药物研究所
通讯作者Bi, Yong
作者单位1.Monash Suzhou Res Inst, Suzhou, Jiangsu, Peoples R China
2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China
3.Tongji Univ, Shanghai Peoples Hosp 4, Translat Res Inst Brain & Brain Like Intelligence, Sch Med, Shanghai, Peoples R China
4.Tongji Univ, Shanghai Tongji Hosp, Sch Med, Dept Neurol, Shanghai, Peoples R China
5.Shanghai Univ Med & Hlth Sci, Zhoupu Hosp, Dept Neurol, 1500 Zhouyuan Rd,Pudong New Area, Shanghai 201318, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Zhilin,Liu, Yuan,Zhao, Jinyue,et al. PHLPP1 deficiency alleviates dopaminergic neurodegeneration and represses neuroinflammation in Parkinson's disease[J]. BEHAVIORAL AND BRAIN FUNCTIONS,2025,21(1):12.
APA Chen, Zhilin.,Liu, Yuan.,Zhao, Jinyue.,Zhou, Xin.,Han, Yudi.,...&Bi, Yong.(2025).PHLPP1 deficiency alleviates dopaminergic neurodegeneration and represses neuroinflammation in Parkinson's disease.BEHAVIORAL AND BRAIN FUNCTIONS,21(1),12.
MLA Chen, Zhilin,et al."PHLPP1 deficiency alleviates dopaminergic neurodegeneration and represses neuroinflammation in Parkinson's disease".BEHAVIORAL AND BRAIN FUNCTIONS 21.1(2025):12.

入库方式： OAI收割

来源：上海药物研究所

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