您的位置: 首页 > 2023年12月 第54卷 第12期 > 文字全文
2023年7月 第38卷 第7期11
目录

小胶质细胞在帕金森病中的双向作用:神经保护和疾病恶化

Microglial involvement in Parkinson's disease progression:Neuroprotection and disease aggravation

来源期刊: 广州医药 | 1-12 发布时间:2024-01-10 收稿时间:2025/11/13 18:27:45 阅读量:72
作者:
关键词:
帕金森病小胶质细胞神经毒素模型α-突触核蛋白模型LRRK2模型
Parkinson's diseasemicroglianeurotoxin modelalpha-synuclein modelLRRK2 model
DOI:
10.3969/j.issn.1000-8535.2023.12.001
收稿时间:
2023-10-05 
修订日期:
 
接收日期:
 
引用总数:
7  
帕金森病(PD)是一种常见的与年龄相关的神经退行性疾病,其特点是黑质致密部内多巴胺能神经元的进行性丢失以及路易小体的积累。多巴胺能神经元的退化导致纹状体的多巴胺水平降低,最终出现静息性震颤、运动迟缓、肌肉僵硬和姿势不稳等运动症状,以及认知能力下降、嗅觉功能受损、精神异常和睡眠障碍等非运动症状。由于人口结构转变和全球老龄化,PD的不断增加对患者、家庭和社会构成重大负担。尽管广泛的研究已阐明了PD的病因学和潜在机制,但现有治疗主要集中在症状管理,无法阻止疾病的进展。小胶质细胞作为脑内重要的免疫细胞,对维持中枢神经系统的稳态具有关键作用。本文综述了PD研究,包括其病因学因素、分子机制和现有治疗策略。此外,审视了在PD样模型中涉及小胶质细胞的研究,深入探讨了小胶质细胞在疾病进展中的动态,并探究了小胶质细胞在促进或减轻疾病进展方面所扮演的错综角色。通过这样的探讨,本综述旨在为PD复杂的发病机制提供新的洞见和观点,激发出针对性治疗干预的创新思路。
Parkinson's disease(PD),a prevalent age-related neurodegenerative disorder,is characterized by the progressive loss of dopaminergic neurons within the substantia nigra compacta(SNc)and the accumulation of Lewy bodies.The degeneration of dopaminergic neurons leads to diminished striatal dopamine levels,culminating in motor symptoms such as resting tremors,bradykinesia,muscle rigidity and postural instability,alongside non-motor manifestations encompassing cognitive decline,impaired olfactory function,psychological abnormalities and sleep disturbances.The escalating incidence of PD due to shifting demographics and global aging poses substantial burdens on patients,families and society.Although extensive research has elucidated the etiology and underlying mechanisms of PD,available treatments largely focus on symptom management and lack the capacity to halt disease progression.Microglia,as integral immune cells within the brain,wield pivotal influence over central nervous system homeostasis.This review presents a comprehensive synthesis of PD,encompassing its etiological factors,molecular mechanisms,and existing therapeutic strategies.Furthermore,we scrutinized research involving microglia in PD-like models,delving into the dynamics of microglia in disease progression and probing into the intricate roles that microglia assume in either fostering or mitigating disease advancement.By doing so,this review aims to furnish novel insights and perspectives that shed light on the intricate pathogenesis of PD,potentially sparking innovative concepts for targeted therapeutic interventions.
1、 WANG Q,LIU Y,ZHOU J.Neuroinflammation in Parkinson's disease and its potential as therapeutic target[J].Transl Neurodegener,2015(4):19. WANG Q,LIU Y,ZHOU J.Neuroinflammation in Parkinson's disease and its potential as therapeutic target[J].Transl Neurodegener,2015(4):19.
2、 LEE H J,SUK J E,BAE E J,et al.Clearance and deposition of extracellular alpha-synuclein aggregates in microglia[J].Biochem Biophys Res Commun,2008,372(3):423-428. LEE H J,SUK J E,BAE E J,et al.Clearance and deposition of extracellular alpha-synuclein aggregates in microglia[J].Biochem Biophys Res Commun,2008,372(3):423-428.
3、 STEFANIS L,EMMANOUILIDOU E,PANTAZOPOULOU M,et al.How is alpha-synuclein cleared from the cell?[J].J Neurochem,2019,150(5):577-590. STEFANIS L,EMMANOUILIDOU E,PANTAZOPOULOU M,et al.How is alpha-synuclein cleared from the cell?[J].J Neurochem,2019,150(5):577-590.
4、 XU L,HE D,BAI Y.Microglia-mediated inflammation and neurodegenerative disease[J].Mol Neurobiol,2016,53(10):6709-6715. XU L,HE D,BAI Y.Microglia-mediated inflammation and neurodegenerative disease[J].Mol Neurobiol,2016,53(10):6709-6715.
5、 RENTZOS M,NIKOLAOU C,ANDREADOU E,et al.Circulating interleukin-10 and interleukin-12 in Parkinson's disease[J].Acta Neurol Scand,2009,119(5):332-337. RENTZOS M,NIKOLAOU C,ANDREADOU E,et al.Circulating interleukin-10 and interleukin-12 in Parkinson's disease[J].Acta Neurol Scand,2009,119(5):332-337.
6、 LIU Y,YU L,XU Y,et al.Substantia nigra Smad3 signaling deficiency:relevance to aging and Parkinson's disease and roles of microglia,proinflammatory factors,and MAPK[J].J Neuroinflammation,2020,17(1):342. LIU Y,YU L,XU Y,et al.Substantia nigra Smad3 signaling deficiency:relevance to aging and Parkinson's disease and roles of microglia,proinflammatory factors,and MAPK[J].J Neuroinflammation,2020,17(1):342.
7、 PATEL R K,PRASAD N,KUWAR R,et al.Transforming growth factor-beta 1 signaling regulates neuroinflammation and apoptosis in mild traumatic brain injury[J].Brain Behav Immun,2017(64):244-258. PATEL R K,PRASAD N,KUWAR R,et al.Transforming growth factor-beta 1 signaling regulates neuroinflammation and apoptosis in mild traumatic brain injury[J].Brain Behav Immun,2017(64):244-258.
8、 SPITTAU B,WULLKOPF L,ZHOU X,et al.Endogenous transforming growth factor-beta promotes quiescence of primary microglia in vitro[J].Glia,2013,61(2):287-300. SPITTAU B,WULLKOPF L,ZHOU X,et al.Endogenous transforming growth factor-beta promotes quiescence of primary microglia in vitro[J].Glia,2013,61(2):287-300.
9、 WANG L,GONG X,LIU Y,et al.CD200 maintains the region-specific phenotype of microglia in the midbrain and its role in Parkinson's disease[J].Glia,2020,68(9):1874-1890. WANG L,GONG X,LIU Y,et al.CD200 maintains the region-specific phenotype of microglia in the midbrain and its role in Parkinson's disease[J].Glia,2020,68(9):1874-1890.
10、 COLONNA M,BUTOVSKY O.Microglia function in the central nervous system during health and neurodegeneration[J].Annu Rev Immunol,2017(35):441-468. COLONNA M,BUTOVSKY O.Microglia function in the central nervous system during health and neurodegeneration[J].Annu Rev Immunol,2017(35):441-468.
11、 DU R H,SUN H B,HU Z L,et al.Kir6.1/K-ATP channel modulates microglia phenotypes:implication in Parkinson's disease[J].Cell Death Dis,2018,9(3):404. DU R H,SUN H B,HU Z L,et al.Kir6.1/K-ATP channel modulates microglia phenotypes:implication in Parkinson's disease[J].Cell Death Dis,2018,9(3):404.
12、 MOEHLE M S,WEBBER P J,TSE T,et al.LRRK2 inhibition attenuates microglial inflammatory responses[J].J Neurosci,2012,32(5):1602-1611. MOEHLE M S,WEBBER P J,TSE T,et al.LRRK2 inhibition attenuates microglial inflammatory responses[J].J Neurosci,2012,32(5):1602-1611.
13、 ZIMPRICH A,BISKUP S,LEITNER P,et al.Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology[J].Neuron,2004,44(4):601-607. ZIMPRICH A,BISKUP S,LEITNER P,et al.Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology[J].Neuron,2004,44(4):601-607.
14、 GASSER T.Usefulness of genetic testing in PD and PD trials:A balanced review[J].J Parkinsons Dis,2015,5(2):209-215. GASSER T.Usefulness of genetic testing in PD and PD trials:A balanced review[J].J Parkinsons Dis,2015,5(2):209-215.
15、 SANCHEZ-GUAJARDO V,FEBBRARO F,KIRIK D,et al.Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease[J].PLoS One,2010,5(1):e8784. SANCHEZ-GUAJARDO V,FEBBRARO F,KIRIK D,et al.Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease[J].PLoS One,2010,5(1):e8784.
16、 BARKHOLT P,SANCHEZ-GUAJARDO V,KIRIK D,et al.Long-term polarization of microglia upon α-synuclein overexpression in nonhuman primates[J].Neuroscience,2012(208):85-96. BARKHOLT P,SANCHEZ-GUAJARDO V,KIRIK D,et al.Long-term polarization of microglia upon α-synuclein overexpression in nonhuman primates[J].Neuroscience,2012(208):85-96.
17、 GAO H M,ZHANG F,ZHOU H,et al.Neuroinflammation and α-synuclein dysfunction potentiate each other,driving chronic progression of neurodegeneration in a mouse model of Parkinson's disease[J].Environ Health Perspect,2011,119(6):807-814. GAO H M,ZHANG F,ZHOU H,et al.Neuroinflammation and α-synuclein dysfunction potentiate each other,driving chronic progression of neurodegeneration in a mouse model of Parkinson's disease[J].Environ Health Perspect,2011,119(6):807-814.
18、 WATSON M B,RICHTER F,LEE S K,et al.Regionally-specific microglial activation in young mice over-expressing human wildtype alpha-synuclein[J].Exp Neurol,2012,237(2):318-334. WATSON M B,RICHTER F,LEE S K,et al.Regionally-specific microglial activation in young mice over-expressing human wildtype alpha-synuclein[J].Exp Neurol,2012,237(2):318-334.
19、 WAKAMATSU M,ISHII A,IWATA S,et al.Selective loss of nigral dopamine neurons induced by overexpression of truncated human alpha-synuclein in mice[J].Neurobiol Aging,2008,29(4):574-585. WAKAMATSU M,ISHII A,IWATA S,et al.Selective loss of nigral dopamine neurons induced by overexpression of truncated human alpha-synuclein in mice[J].Neurobiol Aging,2008,29(4):574-585.
20、 Masliah E,Rockenstein E,Veinbergs I,et al.Dopaminergic loss and inclusion body formation in alpha-synuclein mice:Implications for neurodegenerative disorders[J].Science,2000,287(5456):1265-1269. Masliah E,Rockenstein E,Veinbergs I,et al.Dopaminergic loss and inclusion body formation in alpha-synuclein mice:Implications for neurodegenerative disorders[J].Science,2000,287(5456):1265-1269.
21、 MAGEN I,CHESSELET M F.Genetic mouse models of Parkinson's disease The state of the art[J].Prog Brain Res,2010(184):53-87. MAGEN I,CHESSELET M F.Genetic mouse models of Parkinson's disease The state of the art[J].Prog Brain Res,2010(184):53-87.
22、 DAWSON T M,KO H S,DAWSON V L.Genetic animal models of Parkinson's disease[J].Neuron,2010,66(5):646-661. DAWSON T M,KO H S,DAWSON V L.Genetic animal models of Parkinson's disease[J].Neuron,2010,66(5):646-661.
23、 ESCHBACH J,DANZER K M.α-Synuclein in Parkinson's disease:Pathogenic function and translation into animal models[J].Neurodegener Dis,2014,14(1):1-17. ESCHBACH J,DANZER K M.α-Synuclein in Parkinson's disease:Pathogenic function and translation into animal models[J].Neurodegener Dis,2014,14(1):1-17.
24、 KOROS C,SIMITSI A,STEFANIS L.Genetics of Parkinson's Disease:Genotype-phenotype correlations[J].Int Rev Neurobiol,2017(132):197-231. KOROS C,SIMITSI A,STEFANIS L.Genetics of Parkinson's Disease:Genotype-phenotype correlations[J].Int Rev Neurobiol,2017(132):197-231.
25、 WALSH S,FINN D P,DOWD E.Time-course of nigrostriatal neurodegeneration and neuroinflammation in the 6-hydroxydopamine-induced axonal and terminal lesion models of Parkinson's disease in the rat[J].Neuroscience,2011(175):251-261. WALSH S,FINN D P,DOWD E.Time-course of nigrostriatal neurodegeneration and neuroinflammation in the 6-hydroxydopamine-induced axonal and terminal lesion models of Parkinson's disease in the rat[J].Neuroscience,2011(175):251-261.
26、 GAO H M,HONG J S,ZHANG W,et al.Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide:Relevance to the etiology of Parkinson's disease[J].J Neurosci,2003,23(4):1228-1236. GAO H M,HONG J S,ZHANG W,et al.Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide:Relevance to the etiology of Parkinson's disease[J].J Neurosci,2003,23(4):1228-1236.
27、 BARCIA C,SáNCHEZ BAHILLO A,FERNáNDEZ-VILLALBA E,et al.Evidence of active microglia in substantia nigra pars compacta of parkinsonian monkeys 1 year after MPTP exposure[J].Glia,2004,46(4):402-409. BARCIA C,SáNCHEZ BAHILLO A,FERNáNDEZ-VILLALBA E,et al.Evidence of active microglia in substantia nigra pars compacta of parkinsonian monkeys 1 year after MPTP exposure[J].Glia,2004,46(4):402-409.
28、 SMEYNE R J,JACKSON-LEWIS V.The MPTP model of Parkinson's disease[J].Brain Res Mol Brain Res,2005,134(1):57-66. SMEYNE R J,JACKSON-LEWIS V.The MPTP model of Parkinson's disease[J].Brain Res Mol Brain Res,2005,134(1):57-66.
29、 WU D C,JACKSON-LEWIS V,VILA M,et al.Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease[J].J Neurosci,2002,22(5):1763-1771. WU D C,JACKSON-LEWIS V,VILA M,et al.Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease[J].J Neurosci,2002,22(5):1763-1771.
30、 GIULIANI F,HADER W,YONG V W.Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction[J].J Leukoc Biol,2005,78(1):135-143. GIULIANI F,HADER W,YONG V W.Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction[J].J Leukoc Biol,2005,78(1):135-143.
31、 SCHINTU N,FRAU L,IBBA M,et al.Progressive dopaminergic degeneration in the chronic MPTPp mouse model of Parkinson's disease[J].Neurotox Res,2009,16(2):127-139. SCHINTU N,FRAU L,IBBA M,et al.Progressive dopaminergic degeneration in the chronic MPTPp mouse model of Parkinson's disease[J].Neurotox Res,2009,16(2):127-139.
32、 CZ?ONKOWSKA A,KOHUTNICKA M,KURKOWSKA-JASTRZEBSKA I,et al.Microglial reaction in MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)induced Parkinson's disease mice model[J].Neurodegeneration,1996,5(2):137-143. CZ?ONKOWSKA A,KOHUTNICKA M,KURKOWSKA-JASTRZEBSKA I,et al.Microglial reaction in MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)induced Parkinson's disease mice model[J].Neurodegeneration,1996,5(2):137-143.
33、 LANGSTON J W,FORNO L S,TETRUD J,et al.Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure[J].Ann Neurol,1999,46(4):598-605. LANGSTON J W,FORNO L S,TETRUD J,et al.Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure[J].Ann Neurol,1999,46(4):598-605.
34、 HEPPNER F L,RANSOHOFF R M,BECHER B.Immune attack:The role of inflammation in Alzheimer disease[J].Nat Rev Neurosci,2015,16(6):358-372. HEPPNER F L,RANSOHOFF R M,BECHER B.Immune attack:The role of inflammation in Alzheimer disease[J].Nat Rev Neurosci,2015,16(6):358-372.
35、 JOERS V,TANSEY M G,MULAS G,et al.Microglial phenotypes in Parkinson's disease and animal models of the disease[J].Prog Neurobiol,2017(155):57-75. JOERS V,TANSEY M G,MULAS G,et al.Microglial phenotypes in Parkinson's disease and animal models of the disease[J].Prog Neurobiol,2017(155):57-75.
36、 TANSEY M G,GOLDBERG M S.Neuroinflammation in Parkinson's disease:Its role in neuronal death and implications for therapeutic intervention[J].Neurobiol Dis,2010,37(3):510-518. TANSEY M G,GOLDBERG M S.Neuroinflammation in Parkinson's disease:Its role in neuronal death and implications for therapeutic intervention[J].Neurobiol Dis,2010,37(3):510-518.
37、 LIDDELOW S A,GUTTENPLAN K A,CLARKE L E,et al.Neurotoxic reactive astrocytes are induced by activated microglia[J].Nature,2017,541(7638):481-487. LIDDELOW S A,GUTTENPLAN K A,CLARKE L E,et al.Neurotoxic reactive astrocytes are induced by activated microglia[J].Nature,2017,541(7638):481-487.
38、 BOOTH H D E,HIRST W D,WADE-MARTINS R.The role of astrocyte dysfunction in Parkinson's disease pathogenesis[J].Trends Neurosci,2017,40(6):358-370. BOOTH H D E,HIRST W D,WADE-MARTINS R.The role of astrocyte dysfunction in Parkinson's disease pathogenesis[J].Trends Neurosci,2017,40(6):358-370.
39、 A SIERRA,R C PAOLICELLI,H KETTENMANN.Cien A?os de Microglía:Milestones in a Century of Microglial Research[J].Trends Neurosci,2019,42(11):778-792. A SIERRA,R C PAOLICELLI,H KETTENMANN.Cien A?os de Microglía:Milestones in a Century of Microglial Research[J].Trends Neurosci,2019,42(11):778-792.
40、 SCHELTENS P,DE STROOPER B,KIVIPELTO M,et al.Alzheimer's disease[J].Lancet,2021,397(10284):1577-1590. SCHELTENS P,DE STROOPER B,KIVIPELTO M,et al.Alzheimer's disease[J].Lancet,2021,397(10284):1577-1590.
41、 SIERKSMA A,ESCOTT-PRICE V,DE STROOPER B.Translating genetic risk of Alzheimer's disease into mechanistic insight and drug targets[J].Science,2020,370(6512):61-66. SIERKSMA A,ESCOTT-PRICE V,DE STROOPER B.Translating genetic risk of Alzheimer's disease into mechanistic insight and drug targets[J].Science,2020,370(6512):61-66.
42、 PRINZ M,JUNG S,PRILLER J.Microglia biology:One century of evolving concepts[J].Cell,2019,179(2):292-311. PRINZ M,JUNG S,PRILLER J.Microglia biology:One century of evolving concepts[J].Cell,2019,179(2):292-311.
43、 DOORN K J,GOUDRIAAN A,BLITS-HUIZINGA C,et al.Increased amoeboid microglial density in the olfactory bulb of Parkinson's and Alzheimer's patients[J].Brain Pathol,2014,24(2):152-165. DOORN K J,GOUDRIAAN A,BLITS-HUIZINGA C,et al.Increased amoeboid microglial density in the olfactory bulb of Parkinson's and Alzheimer's patients[J].Brain Pathol,2014,24(2):152-165.
44、 NAVARRO V,SANCHEZ-MEJIAS E,JIMENEZ S,et al.Microglia in Alzheimer's disease:Activated,dysfunctional or degenerative[J].Front Aging Neurosci,2018(10):140. NAVARRO V,SANCHEZ-MEJIAS E,JIMENEZ S,et al.Microglia in Alzheimer's disease:Activated,dysfunctional or degenerative[J].Front Aging Neurosci,2018(10):140.
45、 SPITTAU B.Aging microglia-phenotypes,functions and implications for age-related neurodegenerative diseases[J].Front Aging Neurosci,2017(9):194. SPITTAU B.Aging microglia-phenotypes,functions and implications for age-related neurodegenerative diseases[J].Front Aging Neurosci,2017(9):194.
46、 RAWJI K S,MISHRA M K,MICHAELS N J,et al.Immunosenescence of microglia and macrophages:Impact on the ageing central nervous system[J].Brain,2016,139(Pt 3):653-661. RAWJI K S,MISHRA M K,MICHAELS N J,et al.Immunosenescence of microglia and macrophages:Impact on the ageing central nervous system[J].Brain,2016,139(Pt 3):653-661.
47、 DAVIES D S,MA J,JEGATHEES T,et al.Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer's disease[J].Brain Pathol,2017,27(6):795-808. DAVIES D S,MA J,JEGATHEES T,et al.Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer's disease[J].Brain Pathol,2017,27(6):795-808.
48、 BISHT K,SHARMA K P,LECOURS C,et al.Dark microglia:A new phenotype predominantly associated with pathological states[J].Glia,2016,64(5):826-839. BISHT K,SHARMA K P,LECOURS C,et al.Dark microglia:A new phenotype predominantly associated with pathological states[J].Glia,2016,64(5):826-839.
49、 GRABERT K,MICHOEL T,KARAVOLOS M H,et al.Microglial brain region-dependent diversity and selective regional sensitivities to aging[J].Nat Neurosci,2016,19(3):504-516. GRABERT K,MICHOEL T,KARAVOLOS M H,et al.Microglial brain region-dependent diversity and selective regional sensitivities to aging[J].Nat Neurosci,2016,19(3):504-516.
50、 YIN Z R,RAJ D,SAIEPOUR N,et al.Immune hyperreactivity of Aβ plaque-associated microglia in Alzheimer's disease[J].Neurobiol Aging,2017(55):115-122. YIN Z R,RAJ D,SAIEPOUR N,et al.Immune hyperreactivity of Aβ plaque-associated microglia in Alzheimer's disease[J].Neurobiol Aging,2017(55):115-122.
51、 NGUYEN H M,GR?SSINGER E M,HORIUCHI M,et al.Differential Kv1.3,KCa3.1,and Kir2.1 expression in “classically” and “alternatively” activated microglia[J].Glia,2017,65(1):106-121. NGUYEN H M,GR?SSINGER E M,HORIUCHI M,et al.Differential Kv1.3,KCa3.1,and Kir2.1 expression in “classically” and “alternatively” activated microglia[J].Glia,2017,65(1):106-121.
52、 TAN Y L,YUAN Y,TIAN L.Microglial regional heterogeneity and its role in the brain[J].Mol Psychiatry,2020,25(2):351-367. TAN Y L,YUAN Y,TIAN L.Microglial regional heterogeneity and its role in the brain[J].Mol Psychiatry,2020,25(2):351-367.
53、 MASUDA T,SANKOWSKI R,STASZEWSKI O,et al.Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution[J].Nature,2019,566(7744):388-392. MASUDA T,SANKOWSKI R,STASZEWSKI O,et al.Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution[J].Nature,2019,566(7744):388-392.
54、 UMPIERRE A D,BYSTROM L L,YING Y,et al.Microglial calcium signaling is attuned to neuronal activity in awake mice[J].Elife,2020(9):e56502. UMPIERRE A D,BYSTROM L L,YING Y,et al.Microglial calcium signaling is attuned to neuronal activity in awake mice[J].Elife,2020(9):e56502.
55、 STOWELL R D,SIPE G O,DAWES R P,et al.Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex[J].Nat Neurosci,2019,22(11):1782-1792. STOWELL R D,SIPE G O,DAWES R P,et al.Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex[J].Nat Neurosci,2019,22(11):1782-1792.
56、 LIU Y U,YING Y,LI Y,et al.Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling[J].Nat Neurosci,2019,22(11):1771-1781. LIU Y U,YING Y,LI Y,et al.Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling[J].Nat Neurosci,2019,22(11):1771-1781.
57、 NIMMERJAHN A,KIRCHHOFF F,HELMCHEN F.Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo[J].Science,2005,308(5726):1314-1318. NIMMERJAHN A,KIRCHHOFF F,HELMCHEN F.Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo[J].Science,2005,308(5726):1314-1318.
58、 HANISCH U K,KETTENMANN H.Microglia:active sensor and versatile effector cells in the normal and pathologic brain[J].Nat Neurosci,2007,10(11):1387-1394. HANISCH U K,KETTENMANN H.Microglia:active sensor and versatile effector cells in the normal and pathologic brain[J].Nat Neurosci,2007,10(11):1387-1394.
59、 PAOLICELLI R C.Microglia states and nomenclature:A field at its crossroads[J].Neuron,2022,110(21):3458-3483. PAOLICELLI R C.Microglia states and nomenclature:A field at its crossroads[J].Neuron,2022,110(21):3458-3483.
60、 HAMMOND T R,ROBINTON D,STEVENS B.Microglia and the Brain:Complementary partners in development and disease[J].Annu Rev Cell Dev Biol,2018(34):523-544. HAMMOND T R,ROBINTON D,STEVENS B.Microglia and the Brain:Complementary partners in development and disease[J].Annu Rev Cell Dev Biol,2018(34):523-544.
61、 LI X,LI Y,JIN Y,et al.Transcriptional and epigenetic decoding of the microglial aging process[J].Nat Aging,2023,3(10):1288-1311. LI X,LI Y,JIN Y,et al.Transcriptional and epigenetic decoding of the microglial aging process[J].Nat Aging,2023,3(10):1288-1311.
62、 PLUVINAGE J V,HANEY M S,SMITH B A H,et al.CD22 blockade restores homeostatic microglial phagocytosis in ageing brains[J].Nature,2019,568(7751):187-192. PLUVINAGE J V,HANEY M S,SMITH B A H,et al.CD22 blockade restores homeostatic microglial phagocytosis in ageing brains[J].Nature,2019,568(7751):187-192.
63、 SALTER M W,STEVENS B.Microglia emerge as central players in brain disease[J].Nat Med,2017,23(9):1018-1027. SALTER M W,STEVENS B.Microglia emerge as central players in brain disease[J].Nat Med,2017,23(9):1018-1027.
64、 MORSCH M,RADFORD R,LEE A,et al.In vivo characterization of microglial engulfment of dying neurons in the zebrafish spinal cord[J].Front Cell Neurosci,2015(9):321. MORSCH M,RADFORD R,LEE A,et al.In vivo characterization of microglial engulfment of dying neurons in the zebrafish spinal cord[J].Front Cell Neurosci,2015(9):321.
65、 HUANG L,JIN J,CHEN K,et al.BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury[J].PLoS Biol,2021,19(7):e3001337. HUANG L,JIN J,CHEN K,et al.BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury[J].PLoS Biol,2021,19(7):e3001337.
66、 YAN Y P,LANG B T,VEMUGANTI R,et al.Galectin-3 mediates post-ischemic tissue remodeling[J].Brain Res,2009 (1288):116-124. YAN Y P,LANG B T,VEMUGANTI R,et al.Galectin-3 mediates post-ischemic tissue remodeling[J].Brain Res,2009 (1288):116-124.
67、 GINHOUX F,GRETER M,LEBOEUF M,et al.Fate mapping analysis reveals that adult microglia derive from primitive macrophages[J].Science,2010,330(6005):841-845. GINHOUX F,GRETER M,LEBOEUF M,et al.Fate mapping analysis reveals that adult microglia derive from primitive macrophages[J].Science,2010,330(6005):841-845.
68、 SIERRA A,de CASTRO F,DEL RíO-HORTEGA J,et al.The “Big-Bang” for modern glial biology:Translation and comments on Pío del Río-Hortega 1919 series of papers on microglia[J].Glia,2016,64(11):1801-1840. SIERRA A,de CASTRO F,DEL RíO-HORTEGA J,et al.The “Big-Bang” for modern glial biology:Translation and comments on Pío del Río-Hortega 1919 series of papers on microglia[J].Glia,2016,64(11):1801-1840.
69、 van HOVE H,MARTENS L,SCHEYLTJENS I,et al.A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment[J].Nat Neurosci,2019,22(6):1021-1035. van HOVE H,MARTENS L,SCHEYLTJENS I,et al.A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment[J].Nat Neurosci,2019,22(6):1021-1035.
70、 MRDJEN D,PAVLOVIC A,HARTMANN F J,et al.High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health,aging,and dsease[J].Immunity,2018,48(2):380-395.e6. MRDJEN D,PAVLOVIC A,HARTMANN F J,et al.High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health,aging,and dsease[J].Immunity,2018,48(2):380-395.e6.
71、 TAN Y Y,JENNER P,CHEN S D.Monoamine Oxidase-B inhibitors for the treatment of Parkinson's disease:Past,present,and future[J].J Parkinsons Dis,2022,12(2):477-493. TAN Y Y,JENNER P,CHEN S D.Monoamine Oxidase-B inhibitors for the treatment of Parkinson's disease:Past,present,and future[J].J Parkinsons Dis,2022,12(2):477-493.
72、 MüLLER T.Catechol-O-methyltransferase inhibitors in Parkinson's disease[J].Drugs,2015,75(2):157-174. MüLLER T.Catechol-O-methyltransferase inhibitors in Parkinson's disease[J].Drugs,2015,75(2):157-174.
73、 VOON V,MEHTA A R,HALLETT M.Impulse control disorders in Parkinson's disease:Recent advances[J].Curr Opin Neurol,2011,24(4):324-330. VOON V,MEHTA A R,HALLETT M.Impulse control disorders in Parkinson's disease:Recent advances[J].Curr Opin Neurol,2011,24(4):324-330.
74、 CONNOLLY B S,LANG A E.Pharmacological treatment of Parkinson disease:A review[J].JAMA,2014,311(16):1670-1683. CONNOLLY B S,LANG A E.Pharmacological treatment of Parkinson disease:A review[J].JAMA,2014,311(16):1670-1683.
75、 KWON D K,KWATRA M,WANG J,et al.Levodopa-induced dyskinesia in Parkinson's disease:Pathogenesis and emerging treatment strategies[J].Cells,2022,11(23):3736. KWON D K,KWATRA M,WANG J,et al.Levodopa-induced dyskinesia in Parkinson's disease:Pathogenesis and emerging treatment strategies[J].Cells,2022,11(23):3736.
76、 CHALLIS C,HORI A,SAMPSON T R,et al.Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice[J].Nat Neurosci,2020,23(3):327-336. CHALLIS C,HORI A,SAMPSON T R,et al.Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice[J].Nat Neurosci,2020,23(3):327-336.
77、 OUCHI Y,YAGI S,YOKOKURA M,et al.Neuroinflammation in the living brain of Parkinson's disease[J].Parkinsonism Relat Disord,2009(15 Suppl 3):S200-4. OUCHI Y,YAGI S,YOKOKURA M,et al.Neuroinflammation in the living brain of Parkinson's disease[J].Parkinsonism Relat Disord,2009(15 Suppl 3):S200-4.
78、 MOGI M,HARADA M,KONDO T,et al.Interleukin-1 beta,interleukin-6,epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients[J].Neurosci Lett,1994,180(2):147-150. MOGI M,HARADA M,KONDO T,et al.Interleukin-1 beta,interleukin-6,epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients[J].Neurosci Lett,1994,180(2):147-150.
79、 MOGI M,HARADA M,KONDO T,et al.Transforming growth factor-beta 1 levels are elevated in the striatum and in ventricular cerebrospinal fluid in Parkinson's disease[J].Neurosci Lett,1995,193(2):129-132. MOGI M,HARADA M,KONDO T,et al.Transforming growth factor-beta 1 levels are elevated in the striatum and in ventricular cerebrospinal fluid in Parkinson's disease[J].Neurosci Lett,1995,193(2):129-132.
80、 HAELTERMAN N A,YOON W H,SANDOVAL H,et al.A mitocentric view of Parkinson's disease[J].Annu Rev Neurosci,2014(37):137-159. HAELTERMAN N A,YOON W H,SANDOVAL H,et al.A mitocentric view of Parkinson's disease[J].Annu Rev Neurosci,2014(37):137-159.
81、 SAZANOV L A.The mechanism of coupling between electron transfer and proton translocation in respiratory complex I[J].J Bioenerg Biomembr,2014,46(4):247-253. SAZANOV L A.The mechanism of coupling between electron transfer and proton translocation in respiratory complex I[J].J Bioenerg Biomembr,2014,46(4):247-253.
82、 SURMEIER D J,SCHUMACKER P T.Calcium,bioenergetics,and neuronal vulnerability in Parkinson's disease[J].J Biol Chem,2013,288(15):10736-10741. SURMEIER D J,SCHUMACKER P T.Calcium,bioenergetics,and neuronal vulnerability in Parkinson's disease[J].J Biol Chem,2013,288(15):10736-10741.
83、 DO VAN B,GOUEL F,JONNEAUX A,et al.Ferroptosis,a newly characterized form of cell death in Parkinson's disease that is regulated by PKC[J].Neurobiol Dis,2016(94):169-178. DO VAN B,GOUEL F,JONNEAUX A,et al.Ferroptosis,a newly characterized form of cell death in Parkinson's disease that is regulated by PKC[J].Neurobiol Dis,2016(94):169-178.
84、 DIXON S J,LEMBERG K M,LAMPRECHT M R,et al.Ferroptosis:An iron-dependent form of nonapoptotic cell death[J].Cell,2012,149(5):1060-1072. DIXON S J,LEMBERG K M,LAMPRECHT M R,et al.Ferroptosis:An iron-dependent form of nonapoptotic cell death[J].Cell,2012,149(5):1060-1072.
85、 LEE D H,GOLD R,LINKER R A.Mechanisms of oxidative damage in multiple sclerosis and neurodegenerative diseases:therapeutic modulation via fumaric acid esters[J].Int J Mol Sci,2012,13(9):11783-11803. LEE D H,GOLD R,LINKER R A.Mechanisms of oxidative damage in multiple sclerosis and neurodegenerative diseases:therapeutic modulation via fumaric acid esters[J].Int J Mol Sci,2012,13(9):11783-11803.
86、 BRIEGER K,SCHIAVONE S,MILLER F J Jr,et al.Reactive oxygen species:from health to disease[J].Swiss Med Wkly,2012(142):w13659. BRIEGER K,SCHIAVONE S,MILLER F J Jr,et al.Reactive oxygen species:from health to disease[J].Swiss Med Wkly,2012(142):w13659.
87、 MELKI R.Role of different alpha-synuclein strains in synucleinopathies,similarities with other neurodegenerative diseases[J].J Parkinsons Dis,2015,5(2):217-227. MELKI R.Role of different alpha-synuclein strains in synucleinopathies,similarities with other neurodegenerative diseases[J].J Parkinsons Dis,2015,5(2):217-227.
88、 BURRé J.The synaptic function of α-Synuclein[J].J Parkinsons Dis,2015,5(4):699-713. BURRé J.The synaptic function of α-Synuclein[J].J Parkinsons Dis,2015,5(4):699-713.
89、 ZHU Y G,WANG C Y,YU M,et al.ULK1 and JNK are involved in mitophagy incurred by LRRK2 G2019S expression[J].Protein Cell,2013,4(9):711-721. ZHU Y G,WANG C Y,YU M,et al.ULK1 and JNK are involved in mitophagy incurred by LRRK2 G2019S expression[J].Protein Cell,2013,4(9):711-721.
90、 Pickrell A M,Youle R J.The roles of PINK1,parkin,and mitochondrial fidelity in Parkinson's disease[J].Neuron,2015,85(2):257-273. Pickrell A M,Youle R J.The roles of PINK1,parkin,and mitochondrial fidelity in Parkinson's disease[J].Neuron,2015,85(2):257-273.
91、 KONG S M,CHAN B K,PARK J S,et al.Parkinson's disease-linked human PARK9/ATP13A2 maintains zinc homeostasis and promotes α-Synuclein externalization via exosomes[J].Hum Mol Genet,2014,23(11):2816-2833. KONG S M,CHAN B K,PARK J S,et al.Parkinson's disease-linked human PARK9/ATP13A2 maintains zinc homeostasis and promotes α-Synuclein externalization via exosomes[J].Hum Mol Genet,2014,23(11):2816-2833.
92、 TWIG G,ELORZA A,MOLINA A J,et al.Fission and selective fusion govern mitochondrial segregation and elimination by autophagy[J].EMBO J,2008,27(2):433-446. TWIG G,ELORZA A,MOLINA A J,et al.Fission and selective fusion govern mitochondrial segregation and elimination by autophagy[J].EMBO J,2008,27(2):433-446.
93、 KREBIEHL G,RUCKERBAUER S,BURBULLA L F,et al.Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1[J].PLoS One,2010,5(2):e9367. KREBIEHL G,RUCKERBAUER S,BURBULLA L F,et al.Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1[J].PLoS One,2010,5(2):e9367.
94、 HAUSER D N,HASTINGS T G.Mitochondrial dysfunction and oxidative stress in Parkinson's disease and monogenic parkinsonism[J].Neurobiol Dis,2013(51):35-42. HAUSER D N,HASTINGS T G.Mitochondrial dysfunction and oxidative stress in Parkinson's disease and monogenic parkinsonism[J].Neurobiol Dis,2013(51):35-42.
95、 HEDRICH K,WINKLER S,HAGENAH J,et al.Recurrent LRRK2(Park8)mutations in early-onset Parkinson's disease[J].Mov Disord,2006,21(9):1506-1510. HEDRICH K,WINKLER S,HAGENAH J,et al.Recurrent LRRK2(Park8)mutations in early-onset Parkinson's disease[J].Mov Disord,2006,21(9):1506-1510.
96、 IKEUCHI T,KAKITA A,SHIGA A,et al.Patients homozygous and heterozygous for SNCA duplication in a family with Parkinsonism and dementia[J].Arch Neurol,2008,65(4):514-519. IKEUCHI T,KAKITA A,SHIGA A,et al.Patients homozygous and heterozygous for SNCA duplication in a family with Parkinsonism and dementia[J].Arch Neurol,2008,65(4):514-519.
97、 BORSCHE M,PEREIRA S L,KLEIN C,et al.Mitochondria and Parkinson's disease:Clinical,molecular,and translational aspects[J].J Parkinsons Dis,2021,11(1):45-60. BORSCHE M,PEREIRA S L,KLEIN C,et al.Mitochondria and Parkinson's disease:Clinical,molecular,and translational aspects[J].J Parkinsons Dis,2021,11(1):45-60.
98、 TANNER C M.Epidemiology of Parkinson's disease[J].Neurol Clin,1992,10(2):317-329. TANNER C M.Epidemiology of Parkinson's disease[J].Neurol Clin,1992,10(2):317-329.
99、 LANGSTON J W,BALLARD P,TETRUD J W,et al.Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis[J].Science,1983,219(4587):979-980. LANGSTON J W,BALLARD P,TETRUD J W,et al.Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis[J].Science,1983,219(4587):979-980.
100、 MARRAS C,CANNING C G,GOLDMAN S M.Environment,lifestyle,and Parkinson's disease:Implications for prevention in the next decade[J].Mov Disord,2019,34(6):801-811. MARRAS C,CANNING C G,GOLDMAN S M.Environment,lifestyle,and Parkinson's disease:Implications for prevention in the next decade[J].Mov Disord,2019,34(6):801-811.
101、 BADANJAK K,FIXEMER S,SMAJI? S,et al.The contribution of microglia to neuroinflammation in Parkinson's disease[J].Int J Mol Sci,2021,22(9):4676. BADANJAK K,FIXEMER S,SMAJI? S,et al.The contribution of microglia to neuroinflammation in Parkinson's disease[J].Int J Mol Sci,2021,22(9):4676.
102、 LANG A E,LOZANO A M.Parkinson's disease.First of two parts[J].N Engl J Med,1998,339(15):1044-1053. LANG A E,LOZANO A M.Parkinson's disease.First of two parts[J].N Engl J Med,1998,339(15):1044-1053.
103、 CHOU K L,STACY M,SIMUNI T,et al.The spectrum of“off”in Parkinson's disease:What have we learned over 40 years?[J].Parkinsonism Relat Disord,2018(51):9-16. CHOU K L,STACY M,SIMUNI T,et al.The spectrum of“off”in Parkinson's disease:What have we learned over 40 years?[J].Parkinsonism Relat Disord,2018(51):9-16.
104、 KRISMER F,PINTER B,MUELLER C,et al.Sniffing the diagnosis:Olfactory testing in neurodegenerative Parkinsonism[J].Parkinsonism Relat Disord,2017(35):36-41. KRISMER F,PINTER B,MUELLER C,et al.Sniffing the diagnosis:Olfactory testing in neurodegenerative Parkinsonism[J].Parkinsonism Relat Disord,2017(35):36-41.
105、 RIZZO G,COPETTI M,ARCUTI S,et al.Accuracy of clinical diagnosis of Parkinson disease:A systematic review and meta-analysis[J].Neurology,2016,86(6):566-576. RIZZO G,COPETTI M,ARCUTI S,et al.Accuracy of clinical diagnosis of Parkinson disease:A systematic review and meta-analysis[J].Neurology,2016,86(6):566-576.
106、 KHOO T K,YARNALL A J,DUNCAN G W,et al.The spectrum of nonmotor symptoms in early Parkinson disease[J].Neurology,2013,80(3):276-281. KHOO T K,YARNALL A J,DUNCAN G W,et al.The spectrum of nonmotor symptoms in early Parkinson disease[J].Neurology,2013,80(3):276-281.
107、 XU D C,CHEN Y,XU Y,et al.Signaling pathways in Parkinson's disease:molecular mechanisms and therapeutic interventions[J].Signal Transduct Target Ther,2023,8(1):73. XU D C,CHEN Y,XU Y,et al.Signaling pathways in Parkinson's disease:molecular mechanisms and therapeutic interventions[J].Signal Transduct Target Ther,2023,8(1):73.
108、 HIRSCH E C,ORIEUX G,MURIEL M P,et al.Nondopaminergic neurons in Parkinson's disease[J].Adv Neurol,2003(91):29-37. HIRSCH E C,ORIEUX G,MURIEL M P,et al.Nondopaminergic neurons in Parkinson's disease[J].Adv Neurol,2003(91):29-37.
109、 ARMSTRONG M J,OKUN M S.Diagnosis and treatment of parkinson disease:A review[J].JAMA,2020,323(6):548-560. ARMSTRONG M J,OKUN M S.Diagnosis and treatment of parkinson disease:A review[J].JAMA,2020,323(6):548-560.
110、 ASCHERIO A,SCHWARZSCHILD M A.The epidemiology of Parkinson's disease:Risk factors and prevention[J].Lancet Neurol,2016,15(12):1257-1272. ASCHERIO A,SCHWARZSCHILD M A.The epidemiology of Parkinson's disease:Risk factors and prevention[J].Lancet Neurol,2016,15(12):1257-1272.
111、 GBD 2016 Parkinson's Disease Collaborators.Global,regional,and national burden of Parkinson's disease,1990-2016:A systematic analysis for the Global Burden of Disease Study 2016BD 2016 Parkinson's Disease Collaborators.Global,regional,and national burden of Parkinson's disease,1990-2016:A systematic analysis for the Global Burden of Disease Study 2016[J].Lancet Neurol,2018,17(11):939-953. GBD 2016 Parkinson's Disease Collaborators.Global,regional,and national burden of Parkinson's disease,1990-2016:A systematic analysis for the Global Burden of Disease Study 2016BD 2016 Parkinson's Disease Collaborators.Global,regional,and national burden of Parkinson's disease,1990-2016:A systematic analysis for the Global Burden of Disease Study 2016[J].Lancet Neurol,2018,17(11):939-953.
1、贾文.白杨素脂质体制备及其体外药理活性评价与在体肠吸收特性研究[D].安徽中医药大学,2024.DOI:10.26922/d.cnki.ganzc.2024.000388. 贾文.白杨素脂质体制备及其体外药理活性评价与在体肠吸收特性研究[D].安徽中医药大学,2024.DOI:10.26922/d.cnki.ganzc.2024.000388.
2、谢文梦.小胶质细胞TFE3介导的神经炎症在帕金森病模型中的作用及机制研究[D].河北医科大学,2024.DOI:10.27111/d.cnki.ghyku.2024.001937. 谢文梦.小胶质细胞TFE3介导的神经炎症在帕金森病模型中的作用及机制研究[D].河北医科大学,2024.DOI:10.27111/d.cnki.ghyku.2024.001937.
3、钟彩玲.DMD对脂多糖诱导的神经炎症的作用及其机制的研究[D].赣南医科大学,2025.DOI:10.27959/d.cnki.ggnyx.2025.000295. 钟彩玲.DMD对脂多糖诱导的神经炎症的作用及其机制的研究[D].赣南医科大学,2025.DOI:10.27959/d.cnki.ggnyx.2025.000295.
4、徐龚钦钰.血流限制训练对去卵巢小鼠抑郁样行为的影响[D].江汉大学,2025.DOI:10.27800/d.cnki.gjhdx.2025.000269. 徐龚钦钰.血流限制训练对去卵巢小鼠抑郁样行为的影响[D].江汉大学,2025.DOI:10.27800/d.cnki.gjhdx.2025.000269.
5、卜诗淼,吴晓君,刘勇,等.一种改良的使用玻璃毛细管进行小鼠玻璃体腔注射方法[J].广州医药,2025,56(03):350-355.DOI:10.20223/j.cnki.1000-8535.2025.03.009. 卜诗淼,吴晓君,刘勇,等.一种改良的使用玻璃毛细管进行小鼠玻璃体腔注射方法[J].广州医药,2025,56(03):350-355.DOI:10.20223/j.cnki.1000-8535.2025.03.009.
6、农康,郑艳艳,傅松文,等.锰致小胶质细胞极化机制研究进展[J].应用预防医学,2025,31(03):313-317. 农康,郑艳艳,傅松文,等.锰致小胶质细胞极化机制研究进展[J].应用预防医学,2025,31(03):313-317.
7、高源,彭嘉昕,龙晶晶,等.基于SIRT1/NF-κB炎症通路研究香兰素对帕金森病小胶质细胞M1/M2极化的调节作用[J].转化医学杂志,2025,14(10):137-143. 高源,彭嘉昕,龙晶晶,等.基于SIRT1/NF-κB炎症通路研究香兰素对帕金森病小胶质细胞M1/M2极化的调节作用[J].转化医学杂志,2025,14(10):137-143.
下一篇
出版者信息








《广州医药》公众号
目录