Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease
Open accessAbstract
Activation of microglia by classical inflammatory mediators can convert astrocytes into a neurotoxic A1 phenotype in a variety of neurological diseases 1,2. Development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat these diseases for which there are no disease-modifying therapies. Glucagon-like peptide-1 receptor (GLP1R) agonists have been indicated as potential neuroprotective agents for neurologic disorders such as Alzheimer's disease and Parkinson's disease 3-13. The mechanisms by which GLP1R agonists are neuroprotective are not known. Here we show that a potent, brain-penetrant long-acting GLP1R agonist, NLY01, protects against the loss of dopaminergic neurons and behavioral deficits in the α-synuclein preformed fibril (α-syn PFF) mouse model of sporadic Parkinson's disease 14,15. NLY01 also prolongs the life and reduces the behavioral deficits and neuropathological abnormalities in the human A53T α-synuclein (hA53T) transgenic mouse model of α-synucleinopathy-induced neurodegeneration 16. We found that NLY01 is a potent GLP1R agonist with favorable properties that is neuroprotective through the direct prevention of microglial-mediated conversion of astrocytes to an A1 neurotoxic phenotype. In light of its favorable properties, NLY01 should be evaluated in the treatment of Parkinson's disease and related neurologic disorders characterized by microglial activation.
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.
Integrity signals
Registry
Cites
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.
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?
Twice-weekly treatment with 3 mg/kg of the PEGylated exenatide NLY01 for 5 months reduced IL-1α, TNF-α, and C1q secretion by primary mouse microglia exposed to α-synuclein preformed fibrils, thereby limiting astrocyte conversion to the neurotoxic A1 phenotype.
“Twice-weekly treatment with 3 mg/kg of the PEGylated exenatide NLY01 for 5 months reduced IL-1α, TNF-α, and C1q secretion by primary mouse microglia exposed to α-synuclein preformed fibrils, thereby limiting astrocyte conversion to the neurotoxic A1 phenotype (46).”
From Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits (2025) · cites this paper as [46]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn mouse models of Parkinson's disease induced by either α-synuclein preformed fibrils or α-synuclein overexpression, treatment with 3 mg/kg NLY01 twice weekly for 5 months protected against neurodegeneration, including α-synuclein aggregation and loss of dopaminergic neurons.
“In mouse models of Parkinson’s disease induced by either α-synuclein preformed fibrils or α-synuclein overexpression, treatment with 3 mg/kg NLY01 twice weekly for 5 months protected against neurodegeneration, including α-synuclein aggregation and loss of dopaminergic neurons (46).”
From Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits (2025) · cites this paper as [46]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredReduced PU.1 expression converts microglial cells to a neuroprotective phenotype.
“This effect was propagated to primary astrocytes inducing a neurotoxic reactive gene signature, which was reduced by PU.1 knock-down in LPS-stimulated microglial cells (Fig. 5g), suggesting reduced PU.1 expression converts microglial cells to a neuroprotective phenotype (Joshi et al., 2019; Yun et al., 2018).”
From Alzheimer's-associated PU.1 expression levels regulate microglial inflammatory response (2021) · cites this paper as Yun et al., 2018
The paper reports that inhibiting microglial activation with NLY01 prevents the formation of neurotoxic A1 astrocytes (Abstract; page unavailable). It does not report that reducing PU.1 expression or knocking down PU.1 converts microglia to a neuroprotective phenotype. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThis effect was propagated to primary astrocytes inducing a neurotoxic reactive gene signature, which was reduced by PU.1 knock-down in LPS-stimulated microglial cells.
“This effect was propagated to primary astrocytes inducing a neurotoxic reactive gene signature, which was reduced by PU.1 knock-down in LPS-stimulated microglial cells (Fig. 5g), suggesting reduced PU.1 expression converts microglial cells to a neuroprotective phenotype (Joshi et al., 2019; Yun et al., 2018).”
From Alzheimer's-associated PU.1 expression levels regulate microglial inflammatory response (2021) · cites this paper as Yun et al., 2018
The passage on astrocyte experiments (section labeled Abstract; no page given) reports that conditioned medium from α-syn PFF-treated microglia induces neurotoxic A1 markers in astrocytes. It reports that NLY01 prevents this conversion, not that PU.1 knock-down reduces a reactive gene signature in LPS-stimulated microglia. The latter, more specific part of the attributed claim is unsupported by this paper. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNLY01, a GLP-1 receptor agonist, protects dopaminergic neurons from inflammatory responses elicited by glial cells, and has been enrolled in a Phase II clinical trial.
“NLY01, a different GLP-1 receptor agonist that can protect dopaminergic neurons from inflammatory responses elicited by glial cells,573 has been enrolled recently in a Phase II clinical trial.”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [573]
Administration of NLY01 prevented microglial activation and reactive astrocyte conversion, protecting against α-synucleinopathy-induced neurodegeneration.
“the administration of NLY01 prevented microglial activation and reactive astrocyte conversion, effectively protecting against α-synucleinopathy-induced neurodegeneration.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [396]
Once A1 astrocytes are induced, they lose their essential functions such as supporting neuronal survival, and they also promote neuroinflammation, which contributes to the progression of neurodegenerative diseases.
“Once A1 astrocytes are induced, they lose their essential functions such as supporting neuronal survival, and they also promote neuroinflammation, which contributes to the progression of neurodegenerative diseases.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [113]
GLP-1 receptor agonists are involved in multiple biological pathways that could be beneficial in Alzheimer's disease including improvement of blood-brain barrier integrity and vascular health, promotion of homeostasis in microglia and astrocytes, positive effects on adaptive immune cells, improvement of synaptic viability, and neuroprotection.
“They are involved in multiple biological pathways that could be beneficial in AD including improvement of BBB integrity and vascular health, promotion of homeostasis in microglia and astrocytes, positive effects on adaptative immune cells (including natural killer cells and activated regulatory T cells), improvement of synaptic viability, and neuroprotection [17–26].”
Preclinical results in murine models treated with GLP-1 receptor agonists suggest that the potential effects of semaglutide in Alzheimer's disease may be exerted via impact on several Alzheimer's disease-related pathophysiologic processes including neuroinflammatory pathways, vascular and blood-brain barrier integrity, reduced synaptic loss, and neuroprotection.
“Preclinical results in murine models treated with GLP-1RAs suggest that the potential effects of semaglutide in AD may be exerted via impact on several AD-related pathophysiologic processes including neuroinflammatory pathways, vascular and BBB integrity, reduced synaptic loss, and neuroprotection [19, 21, 23–26, 46–48];”
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
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971 · see citing works
Self-citationZhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · cited 2× · see citing works
“3b), which differs from the in vivo cortical Glp1r mRNA cellular expression profile 21 .”
Self-citationThe M1 and M2 paradigm of macrophage activation: Time for reassessment
Martinez, F. O., & Gordon, S. (2014) · F1000Prime Reports · doi:10.12703/p6-13 · Cited by 4,689 · see citing works
Luk, K. C., Kehm, V., Carroll, J., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M.-Y. (2012) · Science · doi:10.1126/science.1227157 · Cited by 2,563 · see citing works
Reactive Astrocytes: Production, Function, and Therapeutic Potential
Liddelow, S. A., & Barres, B. A. (2017) · Immunity · doi:10.1016/j.immuni.2017.06.006 · Cited by 2,336 · see citing works
Self-citationGLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus
Meier, J. J. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.140 · Cited by 1,311 · see citing works
Athauda, D., Maclagan, K., Skene, S. S., Bajwa-Joseph, M., Letchford, D., Chowdhury, K., Hibbert, S., Budnik, N., Zampedri, L., Dickson, J., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31585-4 · Cited by 889 · cited 2× · see citing works
“Importantly, the GLP-1R agonist, Exendin-4 may have a disease modifying effect in PD 4,13 .”
Lee, M. K., Stirling, W., Xu, Y., Xu, X., Qui, D., Mandir, A. S., Dawson, T. M., Copeland, N. G., Jenkins, N. A., & Price, D. L. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132197599 · Cited by 824 · see citing works
Self-citationPathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3
Mao, X., Ou, M. T., Karuppagounder, S. S., Kam, T., Yin, X., Xiong, Y., Ge, P., Umanah, G. K. E., Brahmachari, S., Shin, J., et al. (2016) · Science · doi:10.1126/science.aah3374 · Cited by 739 · see citing works
Self-citationVolpicelli-Daley, L. A., Luk, K. C., & Lee, V. M.-Y. (2014) · Nature Protocols · doi:10.1038/nprot.2014.143 · Cited by 731 · see citing works
Li, Y., Perry, T., Kindy, M. S., Harvey, B. K., Tweedie, D., Holloway, H. W., Powers, K., Shen, H., Egan, J. M., Sambamurti, K., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806720106 · Cited by 589 · see citing works
Exenatide and the treatment of patients with Parkinson's disease
Aviles-Olmos, I., Dickson, J., Kefalopoulou, Z., Djamshidian, A., Ell, P., Soderlund, T., Whitton, P., Wyse, R., Isaacs, T., Lees, A., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68295 · Cited by 529 · see citing works
Astrocytic modulation of blood brain barrier: perspectives on Parkinson’s disease
Cabezas, R., Ávila, M. F., González, J., El-Bachá, R. D. S., Báez-Jurado, E., García‐Segura, L. M., Jurado-Coronel, J. C., Capani, F., Cardona‐Gómez, G. P., & Barreto, G. E. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00211 · Cited by 453 · see citing works
A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1
Wang, Y., An, R., Umanah, G. K., Park, H., Nambiar, K., Eacker, S. M., Kim, B., Bao, L., Harraz, M. M., Chang, C., et al. (2016) · Science · doi:10.1126/science.aad6872 · Cited by 421 · see citing works
Self-citationStriatal Blood–Brain Barrier Permeability in Parkinson'S Disease
Gray, M. T., & Woulfe, J. M. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.32 · Cited by 409 · see citing works
Athauda, D., & Foltynie, T. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.01.013 · Cited by 383 · see citing works
Polinski, N. K., Volpicelli-Daley, L. A., Sortwell, C. E., Luk, K. C., Cremades, N., Gottler, L. M., Froula, J., Duffy, M. F., Lee, V. M. Y., Martinez, T. N., et al. (2018) · Journal of Parkinson’s Disease · doi:10.3233/jpd-171248 · Cited by 288 · see citing works
Karuppagounder, S. S., Brahmachari, S., Lee, Y., Dawson, V. L., Dawson, T. M., & Ko, H. S. (2014) · Scientific Reports · doi:10.1038/srep04874 · Cited by 264 · see citing works
Salcedo, I., Tweedie, D., Li, Y., & Greig, N. H. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01971.x · Cited by 263 · see citing works
Kim, S., Moon, M., & Park, S. (2009) · Journal of Endocrinology · doi:10.1677/joe-09-0132 · Cited by 263 · see citing works
Self-citationRole of α-Synuclein in Inducing Innate and Adaptive Immunity in Parkinson Disease
Allen Reish, H. E., & Standaert, D. G. (2015) · Journal of Parkinson’s Disease · doi:10.3233/jpd-140491 · Cited by 244 · see citing works
Harms, A. S., Thome, A. D., Yan, Z., Schonhoff, A. M., Williams, G. P., Li, X., Liu, Y., Qin, H., Benveniste, E. N., & Standaert, D. G. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2017.11.010 · Cited by 236 · see citing works
Andrabi, S. A., Kang, H. C., Haince, J.-F., Lee, Y.-I., Zhang, J., Chi, Z., West, A. B., Koehler, R. C., Poirier, G. G., Dawson, T. M., et al. (2011) · Nature Medicine · doi:10.1038/nm.2387 · Cited by 216 · see citing works
Self-citationParthanatos mediates AIMP2-activated age-dependent dopaminergic neuronal loss
Lee, Y., Karuppagounder, S. S., Shin, J.-H., Lee, Y.-I., Ko, H. S., Swing, D., Jiang, H., Kang, S.-U., Lee, B. D., Kang, H. C., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3500 · Cited by 214 · see citing works
Self-citationTeramoto, S., Miyamoto, N., Yatomi, K., Tanaka, Y., Oishi, H., Arai, H., Hattori, N., & Urabe, T. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.51 · Cited by 201 · see citing works
Activation of tyrosine kinase c-Abl contributes to α-synuclein–induced neurodegeneration
Brahmachari, S., Ge, P., Lee, S. H., Kim, D., Karuppagounder, S. S., Kumar, M., Mao, X., Shin, J. H., Lee, Y., Pletniková, O., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85456 · Cited by 199 · see citing works
Self-citationGBA1 deficiency negatively affects physiological α-synuclein tetramers and related multimers
Kim, S., Yun, S. P., Lee, S., Umanah, G. K. E., Bandaru, V. V. R., Yin, X., Rhee, P., Karuppagounder, S. S., Kwon, S., Lee, H., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700465115 · Cited by 179 · see citing works
Self-citationPanicker, N., Saminathan, H., Jin, H., Neal, M., Harischandra, D. S., Gordon, R., Kanthasamy, K. A., Lawana, V., Sarkar, S., Luo, J. D., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0302-15.2015 · Cited by 163 · see citing works
Self-citationLi, Y., Chigurupati, S., Holloway, H. W., Mughal, M. R., Tweedie, D., Bruestle, D. A., Mattson, M. P., Wang, Y., Harvey, B. K., Ray, B., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032008 · Cited by 131 · see citing works
Lee, C., Jeon, S. J., Cho, K. S., Moon, E., Sapkota, A., Jun, H., Ryu, J. H., & Choi, J. W. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0550-2 · Cited by 126 · see citing works
Glucagon‐like peptide 1 receptor stimulation as a means of neuroprotection
Harkavyi, A., & Whitton, P. S. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00486.x · Cited by 125 · see citing works
Li, Y., Bader, M., Tamargo, I. A., Rubovitch, V., Tweedie, D., Pick, C. G., & Greig, N. H. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13169 · Cited by 103 · see citing works
Ji, C., Xue, G., Cao, L., Feng, P., Li, D., Li, L., Li, G., & Hölscher, C. (2015) · Brain Research · doi:10.1016/j.brainres.2015.09.035 · Cited by 101 · see citing works
Neurodegenerative phenotypes in an A53T -synuclein transgenic mouse model are independent of LRRK2
Daher, J. P. L., Pletniková, O., Biskup, S., Musso, A., Gellhaar, S., Galter, D., Troncoso, J. C., Lee, M. K., Dawson, T. M., Dawson, V. L., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds057 · Cited by 96 · see citing works
Self-citationRachmany, L., Tweedie, D., Li, Y., Rubovitch, V., Holloway, H. W., Miller, J. P., Hoffer, B. J., Greig, N. H., & Pick, C. G. (2012) · AGE · doi:10.1007/s11357-012-9464-0 · Cited by 95 · see citing works
Non-cell-autonomous Neurotoxicity of α-synuclein Through Microglial Toll-like Receptor 2
Kim, C., Lee, H.-J., Masliah, E., & Lee, S.-J. (2016) · Experimental Neurobiology · doi:10.5607/en.2016.25.3.113 · Cited by 92 · see citing works
Self-citationChen, S., An, F.-M., Yin, L., Liu, A.-R., Yin, D.-K., Yao, W.-B., & Gao, X.-D. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.10.038 · Cited by 64 · see citing works
Gonçalves, A., Lin, C.-M., Muthusamy, A., Ribeiro, C., Ambrósio, A. F., Abcouwer, S. F., Fernandes, R., & Antonetti, D. A. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-19006 · Cited by 64 · see citing works
Tweedie, D., Rachmany, L., Rubovitch, V., Li, Y.-Z., Holloway, H., Lehrmann, E., Zhang, Y.-Q., Becker, K. G., Perez, E. J., Hoffer, B., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.07.489 · Cited by 57 · see citing works
Ventorp, F., Bay-Richter, C., Nagendra, A. S., Janelidze, S., Matsson, V. S., Lipton, J., Nordström, U., Westrin, Å., Brundin, P., & Brundin, L. (2017) · Journal of Parkinson’s Disease · doi:10.3233/jpd-171068 · Cited by 56 · see citing works
Wu, H., Tang, X.-Q., Liu, H., Mao, X.-F., & Wang, Y. (2017) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2017.12.005 · Cited by 54 · see citing works
Self-citationKim, T. H., Jiang, H. H., Lee, S., Youn, Y. S., Park, C. W., Byun, Y., Chen, X. S., & Lee, K. C. (2011) · Bioconjugate Chemistry · doi:10.1021/bc100404x · Cited by 53 · see citing works
Self-citationKim, T. H., Jiang, H. H., Lim, S. M., et al. (2012) · Bioconjugate Chemistry · doi:10.1021/bc300265n · Cited by 51 · see citing works
Gullo, F., Ceriani, M., D’Aloia, A., Wanke, E., Constanti, A., Costa, B., & Lecchi, M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00500 · Cited by 35 · see citing works
Donnelly, K. M., DeLorenzo, O. R., Zaya, A., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/868448 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes
Kwon, H. S., & Koh, S.-H. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00221-2 · Cited by 2,595 · see citing works
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works
GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art
Nauck, M. A., Quast, D. R., Wefers, J., & Meier, J. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101102 · Cited by 1,647 · see citing works
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616 · see citing works
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
Overview of General and Discriminating Markers of Differential Microglia Phenotypes
Jurga, A. M., Paleczna, M., & Kuter, K. Z. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00198 · Cited by 1,000 · see citing works
The Discovery and Development of Liraglutide and Semaglutide
Knudsen, L. B., & Lau, J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00155 · Cited by 970 · see citing works
Inflammation in Parkinson’s Disease: Mechanisms and Therapeutic Implications
Pajares, M., I. Rojo, A., Manda, G., Boscá, L., & Cuadrado, A. (2020) · Cells · doi:10.3390/cells9071687 · Cited by 779 · see citing works
Function and therapeutic value of astrocytes in neurological diseases
Lee, H.-G., Wheeler, M. A., & Quintana, F. J. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00390-x · Cited by 662 · see citing works
Animal models of neurodegenerative diseases
Dawson, T. M., Golde, T. E., & Lagier-Tourenne, C. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0236-8 · Cited by 576 · see citing works
Self-citationParkinson disease and the immune system - Associations, mechanisms and therapeutics
Tan, E.-K., Chao, Y.-X., West, A., Chan, L.-L., Poewe, W., & Jankovic, J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0344-4 · Cited by 457 · see citing works
The neurobiology of long COVID
Monje, M., & Iwasaki, A. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.006 · Cited by 415 · see citing works
Microglia modulate neurodegeneration in Alzheimer’s and Parkinson’s diseases
Bartels, T., De Schepper, S., & Hong, S. (2020) · Science · doi:10.1126/science.abb8587 · Cited by 412 · see citing works
Trial of Lixisenatide in Early Parkinson’s Disease
Meissner, W. G., Remy, P., Giordana, C., Maltête, D., Derkinderen, P., Houéto, J.-L., Anheim, M., Benatru, I., Boraud, T., Brefel-Courbon, C., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2312323 · Cited by 369 · see citing works
Inhibition of Stat3‐mediated astrogliosis ameliorates pathology in an Alzheimer's disease model
Reichenbach, N., Delekate, A., Plescher, M., Schmitt, F., Krauss, S., Blank, N., Halle, A., & Petzold, G. C. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201809665 · Cited by 343 · see citing works
Morphological, cellular and molecular basis of brain infection in COVID-19 patients
Crunfli, F., Carregari, V. C., Veras, F. P., Vendramini, P. H., Valença, A. G. F., Antunes, A. S. L. M., Brandão-Teles, C., da Silva Zuccoli, G., Reis-de-Oliveira, G., Silva-Costa, L. C., et al. (2020) · doi:10.1101/2020.10.09.20207464 · Cited by 331 · see citing works
The identity and function of microglia in neurodegeneration
Song, W. M., & Colonna, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0212-1 · Cited by 308 · see citing works
Activation of innate immune cGAS-STING pathway contributes to Alzheimer’s pathogenesis in 5×FAD mice
Xie, X., Ma, G., Li, X., Zhao, J., Zhao, Z., & Zeng, J. (2023) · Nature Aging · doi:10.1038/s43587-022-00337-2 · Cited by 292 · see citing works
Kopp, K. O., Glotfelty, E. J., Li, Y., & Greig, N. H. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106550 · Cited by 298 · see citing works
Upadhya, R., Zingg, W., Shetty, S., & Shetty, A. K. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.04.017 · Cited by 282 · see citing works
Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
Guttenplan, K. A., Weigel, M. K., Adler, D. I., Couthouis, J., Liddelow, S. A., Gitler, A. D., & Barres, B. A. (2020) · Nature Communications · doi:10.1038/s41467-020-17514-9 · Cited by 278 · see citing works
Self-citationFernandez, C. G., Hamby, M. E., McReynolds, M. L., & Ray, W. J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00014 · Cited by 277 · see citing works
Ceyzériat, K., Ben Haim, L., Denizot, A., Pommier, D., Matos, M., Guillemaud, O., Palomares, M.-A., Abjean, L., Petit, F., Gipchtein, P., et al. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0606-1 · Cited by 256 · see citing works
Reich, N., & Hölscher, C. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.970925 · Cited by 248 · see citing works
STING mediates neurodegeneration and neuroinflammation in nigrostriatal α-synucleinopathy
Hinkle, J. T., Patel, J., Panicker, N., Karuppagounder, S. S., Biswas, D., Belingon, B., Chen, R., Brahmachari, S., Pletnikova, O., Troncoso, J. C., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2118819119 · Cited by 240 · see citing works
Self-citationDiabetes medications and risk of Parkinson’s disease: a cohort study of patients with diabetes
Brauer, R., Wei, L., Ma, T., Athauda, D., Girges, C., Vijiaratnam, N., Auld, G., Whittlesea, C., Wong, I., & Foltynie, T. (2020) · Brain · doi:10.1093/brain/awaa262 · Cited by 233 · see citing works
Microglia and Astrocytes in Disease: Dynamic Duo or Partners in Crime?
Liddelow, S. A., Marsh, S. E., & Stevens, B. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.07.006 · Cited by 226 · see citing works
Self-citationUncovering sex differences of rodent microglia
Han, J., Fan, Y., Zhou, K., Blomgren, K., & Harris, R. A. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02124-z · Cited by 224 · see citing works
Neurotoxic Reactive Astrocytes Drive Neuronal Death after Retinal Injury
Guttenplan, K. A., Stafford, B. K., El-Danaf, R. N., Adler, D. I., Münch, A. E., Weigel, M. K., Huberman, A. D., & Liddelow, S. A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107776 · Cited by 221 · see citing works
Self-citationNørgaard, C. H., Friedrich, S., Hansen, C. T., Gerds, T., Ballard, C., Møller, D. V., Knudsen, L. B., Kvist, K., Zinman, B., Holm, E., et al. (2022) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12268 · Cited by 206 · see citing works
Park, J.-S., Kam, T.-I., Lee, S., Park, H., Oh, Y., Kwon, S.-H., Song, J.-J., Kim, D., Kim, H., Jhaldiyal, A., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01180-z · Cited by 192 · see citing works
Self-citationOutside in: Unraveling the Role of Neuroinflammation in the Progression of Parkinson's Disease
Troncoso-Escudero, P., Parra, A., Nassif, M., & Vidal, R. L. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00860 · Cited by 191 · see citing works
Neuron-Astrocyte Interactions in Parkinson’s Disease
Miyazaki, I., & Asanuma, M. (2020) · Cells · doi:10.3390/cells9122623 · Cited by 186 · see citing works
Antidiabetic agents as a novel treatment for Alzheimer’s and Parkinson’s disease
Nowell, J., Blunt, E., Gupta, D., & Edison, P. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101979 · Cited by 179 · see citing works
Timper, K., del Río-Martín, A., Cremer, A. L., Bremser, S., Alber, J., Giavalisco, P., Varela, L., Heilinger, C., Nolte, H., Trifunovic, A., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.05.001 · Cited by 170 · see citing works
Crapser, J. D., Ochaba, J., Soni, N., Reidling, J. C., Thompson, L. M., & Green, K. N. (2020) · Brain · doi:10.1093/brain/awz363 · Cited by 157 · see citing works
Vijiaratnam, N., Girges, C., Auld, G., McComish, R., King, A., Skene, S. S., Hibbert, S., Wong, A., Melander, S., Gibson, R., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(24)02808-3 · Cited by 181 · see citing works
Cummings, J. L., Atri, A., Feldman, H. H., Hansson, O., Sano, M., Knop, F. K., Johannsen, P., León, T., & Scheltens, P. (2025) · Alzheimer's Research & Therapy · doi:10.1186/s13195-024-01666-7 · Cited by 168 · see citing works
Analyzing microglial phenotypes across neuropathologies: a practical guide
Schwabenland, M., Brück, W., Priller, J., Stadelmann, C., Lassmann, H., & Prinz, M. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02370-8 · Cited by 149 · see citing works
McGarry, A., Rosanbalm, S., Leinonen, M., Olanow, C. W., To, D., Bell, A., Lee, D., Chang, J., Dubow, J., Dhall, R., et al. (2024) · The Lancet Neurology · doi:10.1016/s1474-4422(23)00378-2 · Cited by 153 · see citing works
Self-citationSterling, J. K., Adetunji, M. O., Guttha, S., Bargoud, A. R., Uyhazi, K. E., Ross, A. G., Dunaief, J. L., & Cui, Q. N. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108271 · Cited by 148 · see citing works
Hartmann, K., Sepulveda-Falla, D., Rose, I. V. L., Madore, C., Muth, C., Matschke, J., Butovsky, O., Liddelow, S., Glatzel, M., & Krasemann, S. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0735-1 · Cited by 141 · see citing works
Self-citationAlzheimer's-associated PU.1 expression levels regulate microglial inflammatory response
Pimenova, A. A., Herbinet, M., Gupta, I., Machlovi, S. I., Bowles, K. R., Marcora, E., & Goate, A. M. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105217 · Cited by 141 · see citing works
“1 expression converts microglial cells to a neuroprotective phenotype (Joshi et al., 2019; Yun et al., 2018).”
BackgroundFortin, S. M., Lipsky, R. K., Lhamo, R., Chen, J., Kim, E., Borner, T., Schmidt, H. D., & Hayes, M. R. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay8071 · Cited by 127 · see citing works
Tong, B., Ba, Y., Li, Z., Yang, C., Su, K., Qi, H., Zhang, D., Liu, X., Wu, Y., Chen, Y., et al. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106505 · Cited by 117 · see citing works
Heiss, C. N., Mannerås-Holm, L., Lee, Y. S., Serrano-Lobo, J., Håkansson Gladh, A., Seeley, R. J., Drucker, D. J., Bäckhed, F., & Olofsson, L. E. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109163 · Cited by 114 · see citing works
Self-citationProtective role of IGF-1 and GLP-1 signaling activation in neurological dysfunctions
Bhalla, S., Mehan, S., Khan, A., & Rehman, M. U. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104896 · Cited by 108 · see citing works
Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits
Wong, C. K., & Drucker, D. J. (2025) · Journal of Clinical Investigation · doi:10.1172/jci194751 · Cited by 112 · see citing works
“Twice-weekly treatment with 3 mg/kg of the PEGylated exenatide NLY01 for 5 months reduced IL-1 α , TNF-α , and C1q secretion by primary mouse microglia exposed to α -synuclein preformed fibrils, thereby limiting astrocyte conversion to the neurotoxic A1 phenotype (46).”
Glia in neurodegeneration: Drivers of disease or along for the ride?
Gleichman, A. J., & Carmichael, S. T. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104957 · Cited by 90 · see citing works
Astrocytes in the regulation of cerebrovascular functions
Cohen‐Salmon, M., Slaoui, L., Mazaré, N., Gilbert, A., Oudart, M., Alvear‐Perez, R., Elorza‐Vidal, X., Chever, O., & Boulay, A. (2021) · Glia · doi:10.1002/glia.23924 · Cited by 93 · see citing works
Fang, Y., Ding, X., Zhang, Y., Cai, L., Ge, Y., Ma, K., Xu, R., Li, S., Song, M., Zhu, H., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02389-y · Cited by 96 · see citing works
Dutta, D., Jana, M., Paidi, R. K., Majumder, M., Raha, S., Dasarathy, S., & Pahan, K. (2023) · Journal of Clinical Investigation · doi:10.1172/jci161987 · Cited by 87 · see citing works
Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress
Diz-Chaves, Y., Herrera-Pérez, S., González-Matías, L. C., Lamas, J. A., & Mallo, F. (2020) · Nutrients · doi:10.3390/nu12113304 · Cited by 84 · see citing works
What are activated and reactive glia and what is their role in neurodegeneration?
Bennett, M. L., & Viaene, A. N. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105172 · Cited by 77 · see citing works
Glucagon-like peptide 1 receptor agonist use is associated with reduced risk for glaucoma
Sterling, J., Hua, P., Dunaief, J. L., Cui, Q. N., & VanderBeek, B. L. (2023) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2021-319232 · Cited by 75 · see citing works
RNA-seq and network analysis reveal unique glial gene expression signatures during prion infection
Carroll, J. A., Race, B., Williams, K., Striebel, J., & Chesebro, B. (2020) · Molecular Brain · doi:10.1186/s13041-020-00610-8 · Cited by 66 · see citing works
How glucagon-like peptide 1 receptor agonists work
Andreasen, C. R., Andersen, A., Knop, F. K., & Vilsbøll, T. (2021) · Endocrine Connections · doi:10.1530/ec-21-0130 · Cited by 71 · see citing works
Mitochondrial dysfunction compromises ciliary homeostasis in astrocytes
Ignatenko, O., Malinen, S., Rybas, S., Vihinen, H., Nikkanen, J., Kononov, A., Jokitalo, E. S., Ince-Dunn, G., & Suomalainen, A. (2023) · Journal of Cell Biology · doi:10.1083/jcb.202203019 · Cited by 63 · see citing works
Makarava, N., Chang, J. C.-Y., Molesworth, K., & Baskakov, I. V. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104783 · Cited by 64 · see citing works
Chandra, S., Di Meco, A., Dodiya, H. B., Popovic, J., Cuddy, L. K., Weigle, I. Q., Zhang, X., Sadleir, K., Sisodia, S. S., & Vassar, R. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00635-2 · Cited by 58 · see citing works
Interleukin-6 triggers toxic neuronal iron sequestration in response to pathological α-synuclein
Sterling, J. K., Kam, T.-I., Guttha, S., Park, H., Baumann, B., Mehrabani-Tabari, A. A., Schultz, H., Anderson, B., Alnemri, A., Chou, S.-C., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110358 · Cited by 58 · see citing works
Self-citationThe pleiotropic of GLP-1/GLP-1R axis in central nervous system diseases
Zhang, L., Zhang, W., & Tian, X. (2023) · International Journal of Neuroscience · doi:10.1080/00207454.2021.1924707 · Cited by 54 · see citing works
miR-124: A Promising Therapeutic Target for Central Nervous System Injuries and Diseases
Xu, J., Zheng, Y., Wang, L., Liu, Y., Wang, X., Li, Y., & Chi, G. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-021-01091-6 · Cited by 55 · see citing works
Direct and indirect effects of lipids on microglia function
Leyrolle, Q., Layé, S., & Nadjar, A. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134348 · Cited by 50 · see citing works
Dong, H., Zhang, X., Duan, Y., He, Y., Zhao, J., Wang, Z., Wang, J., Li, Q., Fan, G., Liu, Z., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03070-2 · Cited by 49 · see citing works
Johnson, N. R., Yuan, P., Castillo, E., Lopez, T. P., Yue, W., Bond, A., Rivera, B. M., Sullivan, M. C., Hirouchi, M., Giles, K., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-35753-w · Cited by 46 · see citing works
Genetic risk factors for Alzheimer disease: emerging roles of microglia in disease pathomechanisms
Takatori, S., Wang, W., Iguchi, A., & Tomita, T. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-05542-4_5 · Cited by 44 · see citing works
Li, Z., Chen, X., Vong, J. S. L., Zhao, L., Huang, J., Yan, L. Y. C., Ip, B., Wing, Y. K., Lai, H.-M., Mok, V. C. T., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02208-9 · Cited by 42 · see citing works
Self-citationZhou, L., Xu, Z., Oh, Y., Gamuyao, R., Lee, G., Xie, Y., Cho, H., Lee, S., & Duh, E. J. (2021) · JCI Insight · doi:10.1172/jci.insight.93382 · Cited by 34 · see citing works
Self-citationCo-Culture Models: Key Players in In Vitro Neurotoxicity, Neurodegeneration and BBB Modeling Studies
Monteiro, A. R., Barbosa, D. J., Remião, F., & Silva, R. (2024) · Biomedicines · doi:10.3390/biomedicines12030626 · Cited by 27 · see citing works
Drobny, A., Ngo, P. A., Neurath, M. F., Zunke, F., & López-Posadas, R. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.655123 · Cited by 24 · see citing works
Gharagozloo, M., Galleguillos, D., Jank, L., Sotirchos, E. S., Smith, M. D., Garton, T., Kumar, S., Hussein, O., Potluri, S., Taylor, M., et al. (2023) · Neurotherapeutics · doi:10.1007/s13311-023-01390-4 · Cited by 23 · see citing works
Self-citationPankiewicz, J. E., Lizińczyk, A. M., Franco, L. A., Diaz, J. R., Martá-Ariza, M., & Sadowski, M. J. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01261-z · Cited by 15 · see citing works
<i> Cspg4 <sup>high</sup> </i> microglia contribute to microgliosis during neurodegeneration
Liu, Y.-J., Ding, Y., Yin, Y.-Q., Xiao, H., Hu, G., & Zhou, J.-W. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2210643120 · Cited by 14 · see citing works
Woo, K. A., Jang, Y., Kim, H.-J., & Park, P. J. (2026) · Brain · doi:10.1093/brain/awag130 · Cited by 3 · see citing works
- Authors
- Yun, S. P., Kam, T.-I., Panicker, N., Kim, S., Oh, Y., Park, J.-S., Kwon, S.-H., Park, Y. J., Karuppagounder, S. S., Park, H., Kim, S., Oh, N., Kim, N. A., Lee, S., Brahmachari, S., Mao, X., Lee, J. H., Kumar, M., An, D., Kang, S.-U., Lee, Y., Lee, K. C., Na, D. H., Kim, D., Lee, S. H., Roschke, V. V., Liddelow, S. A., Mari, Z., Barres, B. A., Dawson, V. L., Lee, S., Dawson, T. M., & Ko, H. S.
- Affiliations
- Johns Hopkins University (US)
- University of Alabama at Birmingham (US)
- Samsung Biomedical Research Institute (KR)
- Sungkyunkwan University (KR)
- Chung-Ang University (KR)
- Stanford Medicine (US)
- Corresponding author
- Lee, Saebom
- Lee, Sang Hun
- Lee, Seulki
- Ko, Han Seok
- ORCID
- Yun, Seung Pil
- Kam, Tae-In
- Panicker, Nikhil
- Park, Jong-Sung
- Kwon, Seung-Hwan
- Park, Yong Joo
- Karuppagounder, Senthilkumar S.
- Park, Hyejin
- Kim, Sangjune
- Lee, Saebom
- Brahmachari, Saurav
- Mao, Xiaobo
- Lee, Jun Hee
- Kumar, Manoj
- Lee, Yunjong
- Na, Dong Hee
- Kim, Donghoon
- Liddelow, Shane A.
- Mari, Zoltan
- Barres, Ben A.
- Lee, Seulki
- Dawson, Ted M.
- Ko, Han Seok
- Venue
- Nature Medicine
- Published
- 2018-06-11
- Volume
- 24
- Issue
- 7
- Pages
- 931-938
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6039259
- OpenAlex
- W2807256450
- Cited by
- 1,123
- References
- 45
- Citations by year
- 2026: 95 · 2025: 151 · 2024: 163 · 2023: 147 · 2022: 152 · 2021: 168 · 2020: 130 · 2019: 82 · 2018: 30 · 2012: 2
- FWCI
- 46.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (K01AG056841)
- National Institute of Neurological Disorders and Stroke (R21NS098006, R01NS082205, P50NS038377)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Parkinson's disease, microglia, GLP-1 receptor agonists, neuroprotection, alpha-synuclein, alpha-synuclein preformed fibrils, dopaminergic neuron loss, microglial activation, neuroinflammation
- MeSH terms
- Amyloid, Animals, Astrocytes, Disease Models, Animal, Humans, Mice, Inbred C57BL, Mice, Transgenic, Parkinson Disease, Microglia, Neuroprotective Agents, alpha-Synuclein
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
