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虾青素通过Nrf2/NLRX1通路激活线粒体自噬缓解阿尔茨海默病

Astaxanthin alleviates Alzheimer's disease by activating mitophagy via Nrf2/NLRX1 pathway

来源期刊: 广州医药 | 975-981 发布时间:2025-08-28 收稿时间:2025/11/13 18:52:57 阅读量:16
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关键词:
虾青素阿尔茨海默病线粒体自噬NOD样受体蛋白家族成员X1核因子E2相关因子2
astaxanthinAlzheimer's diseasemitophagyNLRX1Nrf2
DOI:
10.20223/j.cnki.1000-8535.2025.07.018
收稿时间:
2024-12-21 
修订日期:
 
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引用总数:
0  
目的 探讨谷氨酸对HT22细胞线粒体自噬和细胞凋亡的影响,并评估虾青素预处理的保护作用及其分子机制。方法 用谷氨酸及虾青素处理HT22细胞,通过蛋白印迹及聚合酶联反应等评估其对线粒体自噬的影响。结果 谷氨酸处理显著抑制线粒体初级自噬(PINK1、Parkin、pULK1ser555和LC3Ⅱ)和次级自噬(LAMP1和Rab7),上调cleaved Caspase-3的表达(P<0.05)。虾青素预处理减少细胞凋亡,恢复了线粒体自噬,PINK1、Parkin、pULK1ser555和LC3Ⅱ的表达水平上升(分别为2.3倍、2.6倍、83.3%及81.1%)(P<0.05),该作用被自噬抑制剂BafA1阻断。此外,谷氨酸抑制Nrf2核内转移和NLRX1表达,而预处理显著促进Nrf2的核内转移并上调NLRX1,分别上调25.8%、33.2%。生物信息学分析显示NLRX1启动子区域含有3个Nrf2结合位点,提示Nrf2通过调控NLRX1转录活性发挥作用。结论 文章首次揭示虾青素通过Nrf2/NLRX1通路激活线粒体自噬,展现神经保护作用。
Objective To explore the effects of glutamate on mitophagy and apoptosis in HT22 cells and evaluate the protective effects and molecular mechanisms of astaxanthin pretreatment.Methods HT22 cells were treated with glutamate and astaxanthin.The effects on mitophagy were assessed using Western Blot and PCR.Results Glutamate treatment significantly inhibited primary mitophagy(PINK1,Parkin,pULK1ser555 and LC3II)and secondary mitophagy(LAMP1 and Rab7)while upregulating cleaved Caspase-3 expression.Astaxanthin pretreatment notably reduced apoptosis and restored mitophagy,the expression levels of PINK1,Parkin,pULK1Ser555 and LC3II were significantly upregulated(by 2.3-fold,2.6-fold,83.3% and 81.1% respectively,P<0.05),but this effect was blocked by the autophagy inhibitor BafA1.Additionally,glutamate suppressed Nrf2 nuclear translocation and NLRX1 expression,whereas astaxanthin promoted Nrf2 nuclear translocation and increased NLRX1 expression by 25.8% and 33.2%,respectively.Bioinformatics analysis revealed three Nrf2 binding sites in the NLRX1 promoter region,suggesting that Nrf2 may regulate NLRX1 transcriptional activity.Conclusions The study demonstrates that astaxanthin exhibited potential neuroprotective effect by activating mitophagy through the Nrf2/NLRX1 pathway.
1、 SONG Y,LIANG H,LI G,et al.The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn2+ trafficking[J].Autophagy,2024,20(4):809-829. SONG Y,LIANG H,LI G,et al.The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn2+ trafficking[J].Autophagy,2024,20(4):809-829.
2、 YE H,CAI T,SHEN Y,et al.MST1 knockdown inhibits osteoarthritis progression through Parkin-mediated mitophagy and Nrf2/NF-κB signalling pathway[J].J Cell Mol Med,2024,28(11):e18476. YE H,CAI T,SHEN Y,et al.MST1 knockdown inhibits osteoarthritis progression through Parkin-mediated mitophagy and Nrf2/NF-κB signalling pathway[J].J Cell Mol Med,2024,28(11):e18476.
3、 WANG Y,LONG L,LUO Q,et al.Aflatoxin B1 induces ROS-dependent mitophagy by modulating the PINK1/Parkin pathway in HepG2 cells[J].Basic Clin Pharmacol Toxicol,2024,135(2):195-209. WANG Y,LONG L,LUO Q,et al.Aflatoxin B1 induces ROS-dependent mitophagy by modulating the PINK1/Parkin pathway in HepG2 cells[J].Basic Clin Pharmacol Toxicol,2024,135(2):195-209.
4、 IMBEAULT E,MAHVELATI TM,BRAUN R,et al.Nlrx1 regulates neuronal cell death[J].Mol Brain,2014(7):90. IMBEAULT E,MAHVELATI TM,BRAUN R,et al.Nlrx1 regulates neuronal cell death[J].Mol Brain,2014(7):90.
5、 YE X,SUN X,STAROVOYTOV V,et al.Parkin-mediated mitophagy in mutant hAPP neurons and Alzheimer's disease patient brains[J].Hum Mol Genet, 2015,24(10):2938-2951. YE X,SUN X,STAROVOYTOV V,et al.Parkin-mediated mitophagy in mutant hAPP neurons and Alzheimer's disease patient brains[J].Hum Mol Genet, 2015,24(10):2938-2951.
6、 XIE C,AMAN Y,ADRIAANSE B A,et al.Culprit or bystander:Defective mitophagy in Alzheimer's disease[J].Front Cell Dev Biol,2020(7):391. XIE C,AMAN Y,ADRIAANSE B A,et al.Culprit or bystander:Defective mitophagy in Alzheimer's disease[J].Front Cell Dev Biol,2020(7):391.
7、 FANG E F,HOU Y,PALIKARAS K,et al.Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease[J].Nat Neurosci,2019,22(3):401-412. FANG E F,HOU Y,PALIKARAS K,et al.Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease[J].Nat Neurosci,2019,22(3):401-412.
8、 FAROOQUI T,FAROOQUI A.Aging:an important factor for the pathogenesis of neurodegenerative diseases[J].Mech Ageing Dev,2009,130(4):203-215. FAROOQUI T,FAROOQUI A.Aging:an important factor for the pathogenesis of neurodegenerative diseases[J].Mech Ageing Dev,2009,130(4):203-215.
9、 DONG X X,WANG Y,QIN Z H.Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases[J].Acta Pharmacol Sin, 2009,30(4):379-387. DONG X X,WANG Y,QIN Z H.Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases[J].Acta Pharmacol Sin, 2009,30(4):379-387.
10、 CUI X,ZONG S,SONG W,et al.Omaveloxolone ameliorates cognitive dysfunction in APP/PS1 mice by stabilizing the STAT3 pathway[J].Life Sci,2023(335):122261. CUI X,ZONG S,SONG W,et al.Omaveloxolone ameliorates cognitive dysfunction in APP/PS1 mice by stabilizing the STAT3 pathway[J].Life Sci,2023(335):122261.
11、 XU J,ZHOU L,WENG Q,et al.Curcumin analogues attenuate Aβ25-35-induced oxidative stress in PC12 cells via Keap1/Nrf2/HO-1 signaling pathways[J].Chem Biol Interact,2019(305):171-179. XU J,ZHOU L,WENG Q,et al.Curcumin analogues attenuate Aβ25-35-induced oxidative stress in PC12 cells via Keap1/Nrf2/HO-1 signaling pathways[J].Chem Biol Interact,2019(305):171-179.
12、 BAHN G,JO D G.Therapeutic approaches to Alzheimer's disease through modulation of NRF2[J].Neuromolecular Med,2019,21(1):1-11. BAHN G,JO D G.Therapeutic approaches to Alzheimer's disease through modulation of NRF2[J].Neuromolecular Med,2019,21(1):1-11.
13、 RAMSEY C P,GLASS C A,MONTGOMERY M B,et al.Expression of Nrf2 in neurodegenerative diseases[J].J Neuropathol Exp Neurol,2007,66(1):75-85. RAMSEY C P,GLASS C A,MONTGOMERY M B,et al.Expression of Nrf2 in neurodegenerative diseases[J].J Neuropathol Exp Neurol,2007,66(1):75-85.
14、 WEN X,HUANG A,HU J,et al.Neuroprotective effect of astaxanthin against glutamate-induced cytotoxicity in HT22 cells:Involvement of the Akt/GSK-3β pathway[J].Neuroscience,2015(303):558-568. WEN X,HUANG A,HU J,et al.Neuroprotective effect of astaxanthin against glutamate-induced cytotoxicity in HT22 cells:Involvement of the Akt/GSK-3β pathway[J].Neuroscience,2015(303):558-568.
15、 PAJARES M,JIMéNEZ-MORENO N,GARCíA-YAGüE á J,et al.Transcription factor NFE2L2/NRF2 is a regulator of macroautophagy genes[J].Autophagy,2016,12(10):1902-1916. PAJARES M,JIMéNEZ-MORENO N,GARCíA-YAGüE á J,et al.Transcription factor NFE2L2/NRF2 is a regulator of macroautophagy genes[J].Autophagy,2016,12(10):1902-1916.
16、 GILL A J,SMITH M D,GALLEGUILLOS D,et al.NLRX1 limits inflammatory neurodegeneration in the anterior visual pathway[J].J Neuroinflammation, 2025,22(1):21. GILL A J,SMITH M D,GALLEGUILLOS D,et al.NLRX1 limits inflammatory neurodegeneration in the anterior visual pathway[J].J Neuroinflammation, 2025,22(1):21.
17、 NAGAI-SINGER M A,MORRISON H A,ALLEN I C.NLRX1 is a multifaceted and enigmatic regulator of immune system function[J].Front Immunol,2019(10):2419. NAGAI-SINGER M A,MORRISON H A,ALLEN I C.NLRX1 is a multifaceted and enigmatic regulator of immune system function[J].Front Immunol,2019(10):2419.
18、 STOKMAN G,KORS L,BAKKER PJ,et al.NLRX1 dampens oxidative stress and apoptosis in tissue injury via control of mitochondrial activity[J].J Exp Med,2017,214(8):2405-2420. STOKMAN G,KORS L,BAKKER PJ,et al.NLRX1 dampens oxidative stress and apoptosis in tissue injury via control of mitochondrial activity[J].J Exp Med,2017,214(8):2405-2420.
19、 MOORE CB,BERGSTRALH DT,DUNCAN JA,et al.NLRX1 is a regulator of mitochondrial antiviral immunity[J].Nature,2008,451(7178):573-577. MOORE CB,BERGSTRALH DT,DUNCAN JA,et al.NLRX1 is a regulator of mitochondrial antiviral immunity[J].Nature,2008,451(7178):573-577.
20、 ZHANG Y,YAO Y,QIU X,et al.Listeria hijacks host mitophagy through a novel mitophagy receptor to evade killing[J].Nat Immunol, 2019,20(4):433-446. ZHANG Y,YAO Y,QIU X,et al.Listeria hijacks host mitophagy through a novel mitophagy receptor to evade killing[J].Nat Immunol, 2019,20(4):433-446.
21、 FAKHRI S,ANEVA I Y,FARZAEI M H,et al.The neuroprotective effects of astaxanthin:Therapeutic targets and clinical perspective[J].Molecules,2019,24(14):2640. FAKHRI S,ANEVA I Y,FARZAEI M H,et al.The neuroprotective effects of astaxanthin:Therapeutic targets and clinical perspective[J].Molecules,2019,24(14):2640.
22、 KIM S H,KIM H.Astaxanthin modulation of signaling pathways that regulate autophagy[J].Mar Drugs,2019,17(10):546. KIM S H,KIM H.Astaxanthin modulation of signaling pathways that regulate autophagy[J].Mar Drugs,2019,17(10):546.
23、 TAO G,WANG X,WANG J,et al.Dihydro-resveratrol ameliorates NLRP3 inflammasome-mediated neuroinflammation via Bnip3-dependent mitophagy in Alzheimer's disease[J].Br J Pharmacol,2025,182(4):1005-1024. TAO G,WANG X,WANG J,et al.Dihydro-resveratrol ameliorates NLRP3 inflammasome-mediated neuroinflammation via Bnip3-dependent mitophagy in Alzheimer's disease[J].Br J Pharmacol,2025,182(4):1005-1024.
24、 GU Y Y,ZHAO X R,ZHANG N,et al.Mitochondrial dysfunction as a therapeutic strategy for neurodegenerative diseases:Current insights and future directions[J].Ageing Res Rev, 2024(102):102577. GU Y Y,ZHAO X R,ZHANG N,et al.Mitochondrial dysfunction as a therapeutic strategy for neurodegenerative diseases:Current insights and future directions[J].Ageing Res Rev, 2024(102):102577.
25、 袁行勇,姚春,陈炜,等.阿尔茨海默病不同治疗方式研究新进展[J].广州医药,2024,55(3):236-244. 袁行勇,姚春,陈炜,等.阿尔茨海默病不同治疗方式研究新进展[J].广州医药,2024,55(3):236-244.
26、 周宇,张盼盼,蒋怡华,等.社区老人轻度认知功能障碍现状及其影响因素间交互作用分析[J].广州医药, 2023,54(8):52-57. 周宇,张盼盼,蒋怡华,等.社区老人轻度认知功能障碍现状及其影响因素间交互作用分析[J].广州医药, 2023,54(8):52-57.
27、 JIA L,QUAN M,FU Y,et al.Dementia in China:Epidemiology,clinical management,and research advances[J].Lancet Neurol,2020,19(1):81-92. JIA L,QUAN M,FU Y,et al.Dementia in China:Epidemiology,clinical management,and research advances[J].Lancet Neurol,2020,19(1):81-92.
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