CoChat
Sign Up
Cited by 203Neuroinflammation and Neurodegeneration MechanismsAutophagy in Disease and TherapyCalcium signaling and nucleotide metabolism

Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration

Open access
Quick, Joseph D., Silva, Cristian, Wong, Jia Hui, Lim, Kah Leong, Reynolds, Richard, Barron, Anna M., Zeng, Jialiu, Lo, Chih Hung·2023·Journal of Neuroinflammation
DOI 10.1186/s12974-023-02866-yPMC PMC10403868
Open this paper in CoChat — free accountOpen PDF

Abstract

Microglia are the resident innate immune cells in the brain with a major role in orchestrating immune responses. They also provide a frontline of host defense in the central nervous system (CNS) through their active phagocytic capability. Being a professional phagocyte, microglia participate in phagocytic and autophagic clearance of cellular waste and debris as well as toxic protein aggregates, which relies on optimal lysosomal acidification and function. Defective microglial lysosomal acidification leads to impaired phagocytic and autophagic functions which result in the perpetuation of neuroinflammation and progression of neurodegeneration. Reacidification of impaired lysosomes in microglia has been shown to reverse neurodegenerative pathology in Alzheimer’s disease. In this review, we summarize key factors and mechanisms contributing to lysosomal acidification impairment and the associated phagocytic and autophagic dysfunction in microglia, and how these defects contribute to neuroinflammation and neurodegeneration. We further discuss techniques to monitor lysosomal pH and therapeutic agents that can reacidify impaired lysosomes in microglia under disease conditions. Finally, we propose future directions to investigate the role of microglial lysosomal acidification in lysosome–mitochondria crosstalk and in neuron–glia interaction for more comprehensive understanding of its broader CNS physiological and pathological implications.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s12974-023-02866-y

Cites

19 of 19 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 111

  1. [1]Thion MS Ginhoux F Garel S Microglia and early brain development: an intimate journey Science 2018 362 185 189 30309946
  2. [2]Bachiller S Jiménez-Ferrer I Paulus A Yang Y Swanberg M Deierborg T Microglia in neurological diseases: a road map to brain-disease dependent-inflammatory response Front Cell Neurosci 2018 12 488 30618635 PMC6305407
  3. [3]Galloway DA Phillips AEMM Owen DRJJ Moore CS Phagocytosis in the brain: homeostasis and disease Front Immunol 2019 10 790 31040847 PMC6477030
  4. [4]Yu F Wang Y Stetler AR Leak RK Hu X Chen J Phagocytic microglia and macrophages in brain injury and repair CNS Neurosci Ther 2022 28 1279 1293 35751629 PMC9344092
  5. [7]Moehle MS West AB M1 and M2 immune activation in Parkinson’s disease: foe and ally? Neuroscience 2015 302 59 73 25463515 PMC4442748
  6. [8]Paolicelli RC Sierra A Stevens B Tremblay M-E Aguzzi A Ajami B Microglia states and nomenclature: a field at its crossroads Neuron 2022 110 3458 3483 36327895 PMC9999291
  7. [9]O’Connor LM O’Connor BA Lim SB Zeng J Lo CH Integrative multi-omics and systems bioinformatics in translational neuroscience: a data mining perspective J Pharm Anal. 2023 10.1016/j.jpha.2023.06.011 37719197 PMC10499660 · DOI
  8. [11]Iyer H Shen K Meireles AM Talbot WS A lysosomal regulatory circuit essential for the development and function of microglia Sci Adv 2023 8 eabp8321 PMC9432849 36044568
  9. [13]Van Acker ZP Perdok A Bretou M Annaert W The microglial lysosomal system in Alzheimer’s disease: guardian against proteinopathy Ageing Res Rev 2021 71 101444 34391945
  10. [14]Colacurcio DJ Nixon RA Disorders of lysosomal acidification—the emerging role of v-ATPase in aging and neurodegenerative disease Ageing Res Rev 2016 32 75 88 27197071 PMC5112157
  11. [15]Trivedi PC Bartlett JJ Pulinilkunnil T Lysosomal biology and function: modern view of cellular debris bin Cells 2020 9 1131 32375321 PMC7290337
  12. [16]Mosher KI Wyss-Coray T Microglial dysfunction in brain aging and Alzheimer’s disease Biochem Pharmacol 2014 88 594 604 24445162 PMC3972294
  13. [17]Shi F Yang Y Kouadir M Fu Y Yang L Zhou X Inhibition of phagocytosis and lysosomal acidification suppresses neurotoxic prion peptide-induced NALP3 inflammasome activation in BV2 microglia J Neuroimmunol 2013 260 121 125 23680490
  14. [18]Jin MM Wang F Qi D Liu WW Gu C Mao CJ A critical role of autophagy in regulating microglia polarization in neurodegeneration Front Aging Neurosci. 2018 10 378 30515090 PMC6256089
  15. [19]Campagno KE Mitchell CH The P2X7 receptor in microglial cells modulates the endolysosomal axis, autophagy, and phagocytosis Front Cell Neurosci 2021 15 645244 33790743 PMC8005553
  16. [21]Matejuk A Ransohoff RM Crosstalk between astrocytes and microglia: an overview Front Immunol 2020 11 1416 32765501 PMC7378357
  17. [22]Degterev A Ofengeim D Yuan J Targeting RIPK1 for the treatment of human diseases Proc Natl Acad Sci 2019 116 9714 9722 31048504 PMC6525537
  18. [23]Jayaraman A Reynolds R Diverse pathways to neuronal necroptosis in Alzheimer’s disease Eur J Neurosci 2022 56 5428 5441 35377966
  19. [24]Lin M Yu H Xie Q Xu Z Shang P Role of microglia autophagy and mitophagy in age-related neurodegenerative diseases Front Aging Neurosci. 2023 14 1100133 37180741 PMC10169626
  20. [26]Guo X Tang P Chen L Liu P Hou C Zhang X Amyloid β-induced redistribution of transcriptional factor EB and lysosomal dysfunction in primary microglial cells Front Aging Neurosci. 2017 9 228 28769785 PMC5515861
  21. [28]Berglund R Guerreiro-Cacais AO Adzemovic MZ Zeitelhofer M Lund H Ewing E Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation Sci Immunol. 2020 5 eabb5077 33067381
  22. [29]Udeochu JC Shea JM Villeda SA Microglia communication: Parallels between aging and Alzheimer’s disease Clin Exp Neuroimmunol 2016 7 114 125 27840659 PMC5084774
  23. [30]Wolfe MS Structure and function of the γ-secretase complex Biochemistry 2019 58 2953 2966 31198028 PMC6618299
  24. [31]Van Cauwenberghe C Van Broeckhoven C Sleegers K The genetic landscape of Alzheimer disease: clinical implications and perspectives Genet Med 2016 18 421 430 26312828 PMC4857183
  25. [32]Ledo JH Liebmann T Zhang R Chang JC Azevedo EP Wong E Presenilin 1 phosphorylation regulates amyloid-β degradation by microglia Mol Psychiatry 2021 26 5620 5635 32792660 PMC7881060
  26. [33]Lee J Chan SL Mattson MP Adverse effect of a presenilin-1 mutation in microglia results in enhanced nitric oxide and inflammatory cytokine responses to immune challenge in the brain NeuroMolecular Med 2002 2 29 45 12230303
  27. [34]Cao Q Li P Lu J Dheen ST Kaur C Ling EA Nuclear factor-κB/p65 responds to changes in the notch signaling pathway in murine BV-2 cells and in amoeboid microglia in postnatal rats treated with the γ-secretase complex blocker DAPT J Neurosci Res 2010 88 2701 2714 20648656
  28. [35]Lee J-H Yu WH Kumar A Lee S Mohan PS Peterhoff CM Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations Cell 2010 141 1146 1158 20541250 PMC3647462
  29. [38]Bustos V Pulina MV Bispo A Lam A Flajolet M Gorelick FS Phosphorylated presenilin 1 decreases β-amyloid by facilitating autophagosome-lysosome fusion Proc Natl Acad Sci U S A 2017 114 7148 7153 28533369 PMC5502640
  30. [39]Bustos V Pulina MV Kelahmetoglu Y Sinha SC Gorelick FS Flajolet M Bidirectional regulation of Aβ levels by presenilin 1 Proc Natl Acad Sci U S A 2017 114 7142 7147 28533411 PMC5502639
  31. [40]Fung S Smith CL Prater KE Case A Green K Osnis L Early-onset familial Alzheimer disease variant PSEN2 N141I heterozygosity is associated with altered microglia phenotype J Alzheimers Dis 2020 77 675 688 32741831 PMC7592656
  32. [41]Pigino G Pelsman A Mori H Busciglio J Presenilin-1 mutations reduce cytoskeletal association, deregulate neurite growth, and potentiate neuronal dystrophy and tau phosphorylation J Neurosci 2001 21 834 842 11157069 PMC6762317
  33. [42]Behbahani H Shabalina IG Wiehager B Concha H Hultenby K Petrovic N Differential role of Presenilin-1 and -2 on mitochondrial membrane potential and oxygen consumption in mouse embryonic fibroblasts J Neurosci Res 2006 84 891 902 16883555
  34. [44]Orre M Kamphuis W Osborn LM Jansen AHP Kooijman L Bossers K Isolation of glia from Alzheimer’s mice reveals inflammation and dysfunction Neurobiol Aging 2014 35 2746 2760 25002035
  35. [45]Wang W-Y Tan M-S Yu J-T Tan L Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease Ann Transl Med 2015 3 136 26207229 PMC4486922
  36. [46]Abbas N Bednar I Mix E Marie S Paterson D Ljungberg A Up-regulation of the inflammatory cytokines IFN-ɣ; and IL-12 and down-regulation of IL-4 in cerebral cortex regions of APPSWE transgenic mice J Neuroimmunol 2002 126 50 57 12020956
  37. [47]Benzing WC Wujek JR Ward EK Shaffer D Ashe KH Younkin SG Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice Neurobiol Aging 1999 20 581 589 10674423
  38. [48]Urrutia PJ Bórquez DA Núñez MT Inflaming the brain with iron Antioxidants 2021 6 1 27 PMC7825317 33419006
  39. [49]Tansey MG Wallings RL Houser MC Herrick MK Keating CE Joers V Inflammation and immune dysfunction in Parkinson disease Nat Rev Immunol 2022 22 657 673 35246670 PMC8895080
  40. [50]Lema Tomé CM Tyson T Rey NL Grathwohl S Britschgi M Brundin P Inflammation and α-Synuclein’s prion-like behavior in Parkinson’s disease—is there a link? Mol Neurobiol 2013 47 561 574 22544647 PMC3589652
  41. [51]Majumdar A Cruz D Asamoah N Buxbaum A Sohar I Lobel P Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils Mol Biol Cell 2007 18 1490 1496 17314396 PMC1838985
  42. [52]Herber DL Roth LM Wilson D Wilson N Mason JE Morgan D Time-dependent reduction in Aβ levels after intracranial LPS administration in APP transgenic mice Exp Neurol 2004 190 245 253 15473997
  43. [53]Ye X Zhu M Che X Wang H Liang XJ Wu C Lipopolysaccharide induces neuroinflammation in microglia by activating the MTOR pathway and downregulating Vps34 to inhibit autophagosome formation J Neuroinflamm 2020 17 18 PMC6954631 31926553
  44. [54]Festa BP Siddiqi FH Jimenez-Sanchez M Won H Rob M Djajadikerta A Microglial-to-neuronal CCR5 signaling regulates autophagy in neurodegeneration Neuron 2023 111 2021 2037.e12 37105172
  45. [55]Majumdar A Capetillo-Zarate E Cruz D Gouras GK Maxfield FR Degradation of Alzheimer’s amyloid fibrils by microglia requires delivery of CIC-7 to lysosomes Mol Biol Cell 2011 22 1664 1676 21441306 PMC3093319
  46. [56]Boissonneault V Filali M Lessard M Relton J Wong G Rivest S Powerful beneficial effects of macrophage colony-stimulating factor on beta-amyloid deposition and cognitive impairment in Alzheimer’s disease Brain 2009 132 1078 1092 19151372
  47. [57]Lau S-F Fu AKY Ip NY Cytokine signaling convergence regulates the microglial state transition in Alzheimer’s disease Cell Mol Life Sci 2021 78 4703 4712 33847763 PMC8195901
  48. [58]Lauro C Limatola C Metabolic reprograming of microglia in the regulation of the innate inflammatory response Front Immunol 2020 11 493 32265936 PMC7099404
  49. [59]Yambire KF Rostosky C Watanabe T Pacheu-Grau D Torres-Odio S Sanchez-Guerrero A Impaired lysosomal acidification triggers iron deficiency and inflammation in vivo Elife 2019 8 e51031 31793879 PMC6917501
  50. [60]Meng F Fleming BA Jia X Rousek AA Mulvey MA Ward DM Lysosomal iron recycling in mouse macrophages is dependent upon both LcytB and Steap3 reductases Blood Adv 2022 6 1692 1707 34982827 PMC8941456
  51. [61]Gabandé-Rodríguez E Pérez-Cañamás A Soto-Huelin B Mitroi DN Sánchez-Redondo S Martínez-Sáez E Lipid-induced lysosomal damage after demyelination corrupts microglia protective function in lysosomal storage disorders EMBO J 2019 38 e99553 30530526 PMC6331723
  52. [62]Liu L Zhang K Sandoval H Yamamoto S Jaiswal M Sanz E Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration Cell 2015 160 177 190 25594180 PMC4377295
  53. [64]Huang YC Hsu SM Shie FS Shiao YJ Chao L-JJ Chen HW Reduced mitochondria membrane potential and lysosomal acidification are associated with decreased oligomeric Aβ degradation induced by hyperglycemia: a study of mixed glia cultures PLoS ONE 2022 17 e0260966 35073330 PMC8786178
  54. [66]Zhou L-Q Dong M-H Hu Z-W Tang Y Chu Y-H Chen M Staged suppression of microglial autophagy facilitates regeneration in CNS demyelination by enhancing the production of linoleic acid Proc Natl Acad Sci 2023 120 e2209990120 36577069 PMC9910603
  55. [68]Fabia F Shih Feng Y Sidhartha M Abhirami Kannan I Rita M Olena K Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation Acta Neuropathol 2023 145 749 772 37115208 PMC10175346
  56. [69]Parhizkar S Gent G Chen Y Rensing N Gratuze M Strout G Sleep deprivation exacerbates microglial reactivity and Aβ deposition in a TREM2-dependent manner in mice Sci Transl Med. 2023 15 eade6285 37099634 PMC10449561
  57. [70]Zhang T Pang W Feng T Guo J Wu K Nunez Santos M TMEM106B regulates microglial proliferation and survival in response to demyelination Sci Adv 2023 9 eadd2676 37146150 PMC10162677
  58. [71]Tanaka Y Suzuki G Matsuwaki T Hosokawa M Serrano G Beach TG Progranulin regulates lysosomal function and biogenesis through acidification of lysosomes Hum Mol Genet 2017 26 969 988 28073925
  59. [72]Reifschneider A Robinson S van Lengerich B Gnörich J Logan T Heindl S Loss of TREM2 rescues hyperactivation of microglia, but not lysosomal deficits and neurotoxicity in models of progranulin deficiency EMBO J 2022 41 e109108 35019161 PMC8844989
  60. [73]Wu Y Shao W Todd TW Tong J Yue M Koga S Microglial lysosome dysfunction contributes to white matter pathology and TDP-43 proteinopathy in GRN-associated FTD Cell Rep 2021 36 109581 34433069 PMC8491969
  61. [74]Montilla A Mata GP Matute C Domercq M Contribution of P2X4 receptors to CNS function and pathophysiology Int J Mol Sci 2020 21 5562 32756482 PMC7432758
  62. [75]Takenouchi T Nakai M Iwamaru Y Sugama S Tsukimoto M Fujita M The activation of P2X7 receptor impairs lysosomal functions and stimulates the release of autophagolysosomes in microglial cells J Immunol 2009 182 2051 2062 19201858
  63. [76]Vázquez-Villoldo N Domercq M Martín A Llop J Gómez-Vallejo V Matute C P2X4 receptors control the fate and survival of activated microglia Glia 2014 62 171 184 24254916
  64. [77]Kanellopoulos JM Almeida-da-Silva CLC Rüütel Boudinot S Ojcius DM Structural and functional features of the P2X4 receptor: an immunological perspective Front Immunol 2021 12 645834 33897694 PMC8059410
  65. [79]Huang P Zou Y Zhong XZ Cao Q Zhao K Zhu MX P2X4 forms functional ATP-activated cation channels on lysosomal membranes regulated by luminal pH J Biol Chem 2014 289 17658 17667 24817123 PMC4067200
  66. [80]Rahman N Ramos-Espiritu L Milner TA Buck J Levin LR Soluble adenylyl cyclase is essential for proper lysosomal acidification J Gen Physiol 2016 148 325 339 27670898 PMC5037342
  67. [81]Lo CH Sachs JN The role of wild-type tau in Alzheimer’s disease and related tauopathies J life Sci 2020 2 1 17 PMC7929479 33665646
  68. [83]Lo CH Recent advances in cellular biosensor technology to investigate tau oligomerization Bioeng Transl Med 2021 6 e10231 34589603 PMC8459642
  69. [84]Sengupta U Nilson AN Kayed R The role of amyloid-β oligomers in toxicity, propagation, and immunotherapy EBioMedicine 2016 6 42 49 27211547 PMC4856795
  70. [85]Bloom GS Amyloid-β and Tau: the trigger and bullet in Alzheimer disease pathogenesis JAMA Neurol 2014 71 505 508 24493463 PMC12908160
  71. [86]Lo CH Lim CKW Ding Z Wickramasinghe SP Braun AR Ashe KH Targeting the ensemble of heterogeneous tau oligomers in cells: a novel small molecule screening platform for tauopathies Alzheimer’s Dement 2019 15 1489 1502 31653529 PMC7038631
  72. [88]Koh J-Y Kim HN Hwang JJ Kim Y-H Park SE Lysosomal dysfunction in proteinopathic neurodegenerative disorders: possible therapeutic roles of cAMP and zinc Mol Brain 2019 12 18 30866990 PMC6417073
  73. [89]Im E Jiang Y Stavrides P Darji S Erdjument-Bromage H Neubert TA Lysosomal dysfunction in Down Syndrome and Alzheimer mouse models is caused by selective v-ATPase inhibition by Tyr682 phosphorylated APP βCTF bioRxiv. 2022 10.1101/2022.06.02.494546 37494443 PMC10371027 · DOI
  74. [90]Yao XC Xue X Zhang HT Zhu MM Yang XW Wu CF Pseudoginsenoside-F11 alleviates oligomeric β-amyloid-induced endosome-lysosome defects in microglia Traffic 2019 20 61 70 30375163
  75. [92]Jäntti H Sitnikova V Ishchenko Y Shakirzyanova A Giudice L Ugidos IF Microglial amyloid beta clearance is driven by PIEZO1 channels J Neuroinflamm 2022 19 147 PMC9199162 35706029
  76. [93]Haenseler W Zambon F Lee H Vowles J Rinaldi F Duggal G Excess α-synuclein compromises phagocytosis in iPSC-derived macrophages Sci Rep 2017 7 9003 28827786 PMC5567139
  77. [94]Schützmann MP Hasecke F Bachmann S Zielinski M Hänsch S Schröder GF Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting Nat Commun 2021 12 4634 34330900 PMC8324842
  78. [95]Prakash P Jethava KP Korte N Izquierdo P Favuzzi E Rose IVLL Monitoring phagocytic uptake of amyloid β into glial cell lysosomes in real time Chem Sci 2021 12 10901 10918 34476070 PMC8372545
  79. [97]Deus CM Yambire KF Oliveira PJ Raimundo N Mitochondria–lysosome crosstalk: from physiology to neurodegeneration Trends Mol Med 2020 26 71 88 31791731
  80. [98]Stagi M Klein ZA Gould TJ Bewersdorf J Strittmatter SM Lysosome size, motility and stress response regulated by fronto-temporal dementia modifier TMEM106B Mol Cell Neurosci 2014 61 226 240 25066864 PMC4145808
  81. [99]Zigdon H Meshcheriakova A Farfel-Becker T Volpert G Sabanay H Futerman AH Altered lysosome distribution is an early neuropathological event in neurological forms of Gaucher disease FEBS Lett 2017 5 774 783 28186340
  82. [100]Wang F Gómez-Sintes R Boya P Lysosomal membrane permeabilization and cell death Traffic 2018 19 918 931 30125440
  83. [101]Nakanishi H Cathepsin regulation on microglial function Biochim Biophys Acta Proteins Proteom 2020 1868 140465 32526473
  84. [102]Stichel CC Luebbert H Inflammatory processes in the aging mouse brain: participation of dendritic cells and T-cells Neurobiol Aging 2007 28 1507 1521 16959379
  85. [103]Rodríguez-Muela N Hernández-Pinto AM Serrano-Puebla A García-Ledo L Latorre SH de la Rosa EJ Lysosomal membrane permeabilization and autophagy blockade contribute to photoreceptor cell death in a mouse model of retinitis pigmentosa Cell Death Differ 2015 22 476 487 25501597 PMC4326579
  86. [104]García-Sanz P Orgaz L Bueno-Gil G Espadas I Rodríguez-Traver E Kulisevsky J N370S-GBA1 mutation causes lysosomal cholesterol accumulation in Parkinson’s disease Mov Disord 2017 32 1409 1422 28779532
  87. [105]Chikte S Panchal N Warnes G Use of LysoTracker dyes: a flow cytometric study of autophagy Cytometry A 2014 85 169 178 23847175
  88. [106]Yapici NB Bi Y Li P Chen X Yan X Mandalapu SR Highly stable and sensitive fluorescent probes (LysoProbes) for lysosomal labeling and tracking Sci Rep 2015 5 8576 25715948 PMC4341211
  89. [107]Chin MY Ang K-H Davies J Alquezar C Garda VG Rooney B Phenotypic screening using high-content imaging to identify lysosomal pH modulators in a neuronal cell model ACS Chem Neurosci 2022 13 1505 1516 35522480 PMC9121341
  90. [108]Ponsford AH Ryan TA Raimondi A Cocucci E Wycislo SA Fröhlich F Live imaging of intra-lysosome pH in cell lines and primary neuronal culture using a novel genetically encoded biosensor Autophagy 2020 17 1 19 PMC8205096 32515674
  91. [109]Kim M Chen C Yaari Z Frederiksen R Randall E Wollowitz J Nanosensor-based monitoring of autophagy-associated lysosomal acidification in vivo Nat Chem Biol 2023 10.1038/s41589-023-01364-9 37322156 PMC10721723 · DOI
  92. [110]Lo CH Zeng J Defective lysosomal acidification: a new prognostic marker and therapeutic target for neurodegenerative diseases Transl Neurodegener 2023 12 29 37287072 PMC10249214
  93. [111]Zeng J Shirihai OS Grinstaff MW Modulating lysosomal pH: a molecular and nanoscale materials design perspective J life Sci 2020 2 25 37 PMC7781074 33403369
  94. [112]Vest RT Chou C-C Zhang H Haney MS Li L Laqtom NN Small molecule C381 targets the lysosome to reduce inflammation and ameliorate disease in models of neurodegeneration Proc Natl Acad Sci U S A 2022 119 e2121609119 35259016 PMC8931323
  95. [113]Arotcarena MM-L Soria FN Cunha A Doudnikoff E Prévot G Daniel J Acidic nanoparticles protect against α-synuclein-induced neurodegeneration through the restoration of lysosomal function Aging Cell 2022 21 e13584 35318803 PMC9009122
  96. [114]Trudeau KM Colby AH Zeng J Las G Feng JH Grinstaff MW Lysosome acidification by photoactivated nanoparticles restores autophagy under lipotoxicity J Cell Biol 2016 214 25 34 27377248 PMC4932370
  97. [115]Zeng J Martin A Han X Shirihai O Grinstaff M Biodegradable PLGA nanoparticles restore lysosomal acidity and protect neural PC-12 cells against mitochondrial toxicity Ind Eng Chem Res 2019 58 13910 13917 PMC10993316 38576774
  98. [116]Wang B Martini-Stoica H Qi C Lu T-C Wang S Xiong W TFEB-vacuolar ATPase signaling regulates lysosomal function and microglial activation in tauopathy bioRxiv. 2023 10.1101/2023.02.06.527293 37985800 PMC12203451 · DOI
  99. [117]Zeng J Acin-Perez R Assali EA Martin A Brownstein AJ Petcherski A Restoration of lysosomal acidification rescues autophagy and metabolic dysfunction in non-alcoholic fatty liver disease Nat Commun 2023 14 2573 37142604 PMC10160018
  100. [118]Lo CH O’Connor LM Loi GWZ Saipuljumri EN Indajang J Lopes KM Acidic nanoparticles restore lysosomal acidification and rescue metabolic dysfunction in pancreatic β-cells under lipotoxic condition bioRxiv. 2023 10.1101/2023.07.11.548395 38830624 PMC11192035 · DOI
  101. [119]Xu X Moreno S Boye S Wang P Voit B Appelhans D Artificial organelles with digesting characteristics: imitating simplified lysosome- and macrophage-like functions by trypsin-loaded polymersomes Adv Sci 2023 10 2207214 PMC10265080 37076948
  102. [120]Lo CH Zeng J Application of polymersomes in membrane protein study and drug discovery: progress, strategies, and perspectives Bioeng Transl Med 2023 8 e10350 36684106 PMC9842050
  103. [121]Audano M Schneider A Mitro N Mitochondria, lysosomes, and dysfunction: their meaning in neurodegeneration J Neurochem 2018 147 291 309 29804302
  104. [122]Nakanishi H Wu Z Microglia-aging: Roles of microglial lysosome- and mitochondria-derived reactive oxygen species in brain aging Behav Brain Res 2009 201 1 7 19428609
  105. [123]Pitt D Lo CH Gauthier SA Hickman RA Longbrake E Airas LM Toward precision phenotyping of multiple sclerosis Neurol - Neuroimmunol Neuroinflamm 2022 9 e200025 36041861 PMC9427000
  106. [124]Fairley LH Lai KO Wong JH Chong WJ Vincent AS D’Agostino G Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer’s disease Proc Natl Acad Sci 2023 120 e2209177120 36787364 PMC9974442
  107. [125]Ziegenfuss JS Doherty J Freeman MR Distinct molecular pathways mediate glial activation and engulfment of axonal debris after axotomy Nat Neurosci 2012 15 979 987 22706267 PMC4976689
  108. [127]Lo CH Skarica M Mansoor M Bhandarkar S Toro S Pitt D Astrocyte heterogeneity in multiple sclerosis: current understanding and technical challenges Front Cell Neurosci 2021 15 726479 34456686 PMC8385194
  109. [128]Sen MK Mahns DA Coorssen JR Shortland PJ The roles of microglia and astrocytes in phagocytosis and myelination: insights from the cuprizone model of multiple sclerosis Glia 2022 70 1215 1250 35107839 PMC9302634
  110. [130]Delpech J-C Herron S Botros MB Ikezu T Neuroimmune crosstalk through extracellular vesicles in health and disease Trends Neurosci 2019 42 361 372 30926143 PMC6486849
  111. [131]Rueda-Carrasco J Martin-Bermejo MJ Pereyra G Mateo MI Borroto A Brosseron F SFRP1 modulates astrocyte-to-microglia crosstalk in acute and chronic neuroinflammation EMBO Rep 2021 22 e51696 34569685 PMC8567217

Cited by

Sorted by citations

Authors
Quick, J. D., Silva, C., Wong, J. H., Lim, K. L., Reynolds, R., Barron, A. M., Zeng, J., & Lo, C. H.
Affiliations
  • University of Minnesota (US)
  • University of Kelaniya (LK)
  • Nanyang Technological University (SG)
Corresponding author
  • Zeng, Jialiu
  • Lo, Chih Hung
ORCID
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2023-08-05
Volume
20
Issue
1
Pages
185-185
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/s12974-023-02866-y
PMC
PMC10403868
OpenAlex
W4385607049
Cited by
203
References
19
Citations by year
2026: 101 · 2025: 66 · 2024: 31 · 2023: 5
FWCI
5.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • Nanyang Technological University (Presidential Postdoctoral Fellowship (Award Number: 021229-00001))
  • National Medical Research Council (Open Fund Young Investigator Research Grant (OF-YIRG) (Award Number: MOH-001147))
  • Lee Kong Chian School of Medicine, Nanyang Technological University (Dean’s Postdoctoral Fellowship (Award Number: 021207-00001))
  • Momental Foundation (Mistletoe Research Fellowship (Award Number: 022522-00001))
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
microglia, lysosomal acidification, lysosomal pH, neuroinflammation, neurodegeneration, phagocytosis, autophagy, neuron-glia interactions, Alzheimer's disease, lysosomal dysfunction
MeSH terms
Neuroinflammatory Diseases, Alzheimer Disease, Humans, Hydrogen-Ion Concentration, Lysosomes, Microglia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review