Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity
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Abstract
Metabolic coordination between neurons and astrocytes is critical for the health of the brain. However, neuron-astrocyte coupling of lipid metabolism, particularly in response to neural activity, remains largely uncharacterized. Here, we demonstrate that toxic fatty acids (FAs) produced in hyperactive neurons are transferred to astrocytic lipid droplets by ApoE-positive lipid particles. Astrocytes consume the FAs stored in lipid droplets via mitochondrial β-oxidation in response to neuronal activity and turn on a detoxification gene expression program. Our findings reveal that FA metabolism is coupled in neurons and astrocytes to protect neurons from FA toxicity during periods of enhanced activity. This coordinated mechanism for metabolizing FAs could underlie both homeostasis and a variety of disease states of the brain.
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Hyperactive neurons can release APOE-associated fatty acids that are taken up by astrocytes and buffer lipotoxic stress.
“cell culture models have demonstrated that hyperactive neurons can release APOE-associated fatty acids which are taken up by astrocytes and buffer lipotoxic stress35.”
From APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia (2024) · cites this paper as [35]
Injured neurons and oligodendrocytes have a low capacity for consuming FFAs and sequestering them into lipid droplets, making them more vulnerable to lipid-induced cytotoxicity in chronic inflammation.
“Injured neurons and oligodendrocytes have a low capacity for consuming FFAs and sequestering them into LDs61, making them more vulnerable to lipid-induced cytotoxicity in chronic inflammation62,63.”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [63]
ApoE-mediated transport of lipids from neurons to glia is neuroprotective in flies and mammalian cells.
“ApoE-mediated transport of lipids from neurons to glia in flies61 and mammalian cells is neuroprotective62.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [62]
Reactive astrocytes can upregulate VLCFA-rich phosphatidylcholines, which drive the death of neurons and oligodendrocytes, probably via lipoparticle secretion.
“Reactive astrocytes can upregulate VLCFA-rich phosphatidylcholines, which drive the death of neurons and OLs, probably via lipoparticle secretion [415].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [415]
Neuron-astrocyte metabolic coupling mediated by apoE plays an essential role in preventing activity-induced lipotoxicity in neurons.
“This neuron–astrocyte metabolic coupling, mediated by apoE, plays an essential role in preventing activity‐induced lipotoxicity in neurons. 1”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [1]
In the CNS, apoE facilitates the transport of cholesterol and fatty acids between cells, maintaining lipid homeostasis.
“In the CNS, apoE facilitates the transport of cholesterol and FAs between cells, maintaining lipid homeostasis.”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [1]
Astrocytes are critical for maintaining CNS homeostasis, playing essential roles in lipid metabolism and clearance of toxic protein aggregates.
“Astrocytes are critical for maintaining central nervous system (CNS) homeostasis, playing essential roles in lipid metabolism and the clearance of toxic protein aggregates.”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [1]
ApoE transports peroxidized FAs from neuron to astrocyte upon neuronal stimulation.
“recent reports revealed a role of ApoE in transporting peroxidized FAs from neuron to astrocyte upon neuronal stimulation (Ioannou et al., 2019)”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Ioannou et al., 2019
E4 astrocytes have lower ability in uptaking LDL, consistent with a reduced capacity in internalizing FAs.
“Because LDL receptors are involved in neuron-to-astrocyte FA transfer (Ioannou et al., 2019), the lower ability of E4 astrocytes in uptaking LDL (Figure S3E) is consistent with a reduced capacity of E4 astrocytes in internalizing FAs.”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Ioannou et al., 2019
Substantial accumulation of LD-like lipid structures occurs in primary hippocampal neurons under culture conditions without extra NMDA stimulation or oxidative challenge.
“Strikingly, we observed substantial accumulation of LD-like lipid structures in neurons (Figure 1A; days in vitro 8 [DIV8]) under culture conditions without extra NMDA stimulation or oxidative challenge used previously (Ioannou et al., 2019).”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Ioannou et al., 2019
Autophagy contributes to lipid droplet formation in NMDA-stimulated neurons.
“while autophagy contributes to LD formation in NMDA-stimulated neurons (Ioannou et al., 2019)”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Ioannou et al., 2019
Upon oxidative stress or hyperactivity, neurons transfer peroxidized fatty acids to glia via ApoE-positive lipid particles.
“Upon oxidative stress or hyperactivity, neurons transfer peroxidized FAs to glia via ApoE-positive lipid particles (Ioannou et al., 2019).”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Ioannou et al., 2019
Astrocytes store neuron-derived lipids in lipid droplets, which protect against neurotoxicity.
“Other studies demonstrated that lipid peroxides formed in neurons under oxidative or excitotoxic stress can be transported by APOE-lipoproteins to astrocytes; astrocytes store these neuron-derived lipids in LDs, which protect against neurotoxicity and may play a role in detoxifying these deleterious lipid species (Walker et al., 2006; Liu et al., 2015, 2017; Ioannou et al., 2019; Moulton et al., 2”
From APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size (2024) · cites this paper as Ioannou et al., 2019
Lipid peroxides formed in neurons under oxidative or excitotoxic stress can be transported by APOE-lipoproteins to astrocytes.
“Other studies demonstrated that lipid peroxides formed in neurons under oxidative or excitotoxic stress can be transported by APOE-lipoproteins to astrocytes; astrocytes store these neuron-derived lipids in LDs, which protect against neurotoxicity and may play a role in detoxifying these deleterious lipid species (Walker et al., 2006; Liu et al., 2015, 2017; Ioannou et al., 2019; Moulton et al., 2”
From APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size (2024) · cites this paper as Ioannou et al., 2019
Ischemia is correlated with both increased lipid peroxidation and neutral lipid accumulation in the brain.
“Ischemia is correlated with both increased lipid peroxidation and neutral lipid accumulation in the brain (Yoshida et al., 1982; Gasparovic et al., 2001; Ioannou et al., 2019).”
From APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size (2024) · cites this paper as Ioannou et al., 2019
Various studies have shown that lipid droplets influence intercellular communication.
“Various studies have shown that lipid droplets influence intercellular communication13,17,61.”
From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [61]
These genes have been implicated in coordinating lipid and oxidative metabolism between neurons and astrocytes.
“Collectively, these genes have been implicated in the coordination of lipid and oxidative metabolism between neurons and astrocytes30.”
From Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (2020) · cites this paper as [30]
Astrocytes and microglia secrete and degrade a huge array and quantity of lipids.
“these results and those of others demonstrate that astrocytes and microglia secrete and degrade a huge array and quantity of lipids”
From Neurotoxic reactive astrocytes induce cell death via saturated lipids (2021) · cites this paper as [21]
Cites
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
Cutadapt removes adapter sequences from high-throughput sequencing reads
Martin, M. (2011) · EMBnet.journal · doi:10.14806/ej.17.1.200 · Cited by 33,889 · see citing works
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
Li, B., & Dewey, C. N. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-323 · Cited by 22,179 · see citing works
Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556 · see citing works
Trapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 11,930 · see citing works
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,477 · see citing works
Shedding light on the cell biology of extracellular vesicles
van Niel, G., D'Angelo, G., & Raposo, G. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.125 · Cited by 8,369 · see citing works
Ayala, A., Muñoz, M., & Argüelles, S. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/360438 · Cited by 6,557 · see citing works
A guided tour into subcellular colocalization analysis in light microscopy
Bolte, S., & Cordelières, F. (2006) · Journal of Microscopy · doi:10.1111/j.1365-2818.2006.01706.x · Cited by 5,238 · see citing works
Zhang, 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 · see citing works
Ceramide Triggers Budding of Exosome Vesicles into Multivesicular Endosomes
Trajković, K., Hsu, C., Chiantia, S., Rajendran, L., Wenzel, D., Wieland, F., Schwille, P., Brügger, B., & Simons, M. (2008) · Science · doi:10.1126/science.1153124 · Cited by 3,639 · see citing works
Nile red: a selective fluorescent stain for intracellular lipid droplets.
Greenspan, P., Mayer, E. P., & Fowler, S. D. (1985) · The Journal of cell biology · doi:10.1083/jcb.100.3.965 · Cited by 2,543 · see citing works
Huang, D. W., Sherman, B. T., Tan, Q., Collins, J., Alvord, W. G., Roayaei, J., Stephens, R. D., Baseler, M., Lane, H. C., & Lempicki, R. A. (2007) · Genome biology · doi:10.1186/gb-2007-8-9-r183 · Cited by 2,482 · see citing works
Brain energy metabolism: focus on Astrocyte-neuron metabolic cooperation
Bélanger, M., Allaman, I., & Magistretti, P. J. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.016 · Cited by 2,313 · see citing works
Huang, D. W., Sherman, B. T., Tan, Q., Kir, J., Liu, D., Bryant, D., Guo, Y., Stephens, R. M., Baseler, M., Lane, H. C., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm415 · Cited by 2,216 · see citing works
Brefeldin A: insights into the control of membrane traffic and organelle structure.
Klausner, R. D., Donaldson, J. G., & Lippincott‐Schwartz, J. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.116.5.1071 · Cited by 1,852 · see citing works
Self-citationSeiler, A., Schneider, M., Förster, H., Roth, S., Wirth, E. K., Culmsee, C., Plesnila, N., Kremmer, E., Rådmark, O., Wurst, W., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.07.005 · Cited by 1,470 · see citing works
Astrocyte glutamate transport: Review of properties, regulation, and physiological functions
Anderson, C. M., & Swanson, R. A. (2000) · Glia · doi:10.1002/1098-1136(200010)32:1 · Cited by 1,218 · see citing works
Excitotoxicity and stroke: Identifying novel targets for neuroprotection
Lai, T. W., Zhang, S., & Wang, Y. T. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.11.006 · Cited by 1,106 · see citing works
Saturated Reconstruction of a Volume of Neocortex
Kasthuri, N., Hayworth, K. J., Berger, D. R., Schalek, R. L., Conchello, J. A., Knowles-Barley, S., Lee, D., Vázquez-Reina, A., Kaynig, V., Jones, T. R., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.054 · Cited by 1,044 · see citing works
Rambold, A. S., Cohen, S., & Lippincott-Schwartz, J. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.01.029 · Cited by 1,038 · see citing works
Self-citationAlexander, G. M., Rogan, S. C., Abbas, A. I., Armbruster, B. N., Pei, Y., Allen, J., Nonneman, R. J., Hartmann, J. F., Moy, S. S., Nicolelis, M. A. L., et al. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.014 · Cited by 996 · see citing works
Piedrahita, J. A., Zhang, S. H., Hagaman, J. R., Oliver, P. M., & Maeda, N. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.10.4471 · Cited by 944 · see citing works
Glial Lipid Droplets and ROS Induced by Mitochondrial Defects Promote Neurodegeneration
Liu, L., Zhang, K., Sandoval, H., Yamamoto, S., Jaiswal, M., Sanz, E., Li, Z., Hui, J., Graham, B. H., Quintana, A., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.019 · Cited by 876 · see citing works
Lippincott‐Schwartz, J., Yuan, L. C., Tipper, C. H., AMHERDT, M., Orci, L., & Klausner, R. D. (1991) · Cell · doi:10.1016/0092-8674(91)90534-6 · Cited by 836 · see citing works
Self-citationReynolds, I., & Hastings, T. (1995) · The Journal of Neuroscience · doi:10.1523/jneurosci.15-05-03318.1995 · Cited by 777 · see citing works
Pitas, R. E., Boyles, J. K., Lee, S. H., Hui, D., & Weisgraber, K. H. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47945-8 · Cited by 714 · see citing works
Antioxidant Role for Lipid Droplets in a Stem Cell Niche of Drosophila
Bailey, A. P., Koster, G., Guillermier, C., Hirst, E. M. A., MacRae, J. I., Lechène, C., Postle, A. D., & Gould, A. P. (2015) · Cell · doi:10.1016/j.cell.2015.09.020 · Cited by 689 · see citing works
Culturing pyramidal neurons from the early postnatal mouse hippocampus and cortex
Beaudoin, G. M. J., Lee, S.-H., Singh, D., Yuan, Y., Ng, Y., Reichardt, L. F., & Arikkath, J. (2012) · Nature Protocols · doi:10.1038/nprot.2012.099 · Cited by 655 · see citing works
ATP Released by Astrocytes Mediates Glutamatergic Activity-Dependent Heterosynaptic Suppression
Zhang, J.-M., Wang, H.-K., Ye, C.-Q., Ge, W., Chen, Y., Jiang, Z. P., Wu, C.-P., Poo, M.-M., & Duan, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00717-7 · Cited by 632 · see citing works
Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement
Adamsky, A., Kol, A., Kreisel, T., Doron, A., Ozeri-Engelhard, N., Melcer, T., Refaeli, R., Horn, H., Regev, L., Groysman, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.002 · Cited by 631 · see citing works
Nguyen, T. B., Louie, S. M., Daniele, J. R., Tran, Q., Dillin, A., Zoncu, R., Nomura, D. K., & Olzmann, J. A. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.06.003 · Cited by 610 · see citing works
Lipid homeostasis, lipotoxicity and the metabolic syndrome
Unger, R. H., Clark, G. O., Scherer, P. E., & Orci, L. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.10.006 · Cited by 595 · see citing works
Liu, L., MacKenzie, K. R., Putluri, N., Maletić-Savatić, M., & Bellen, H. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.024 · Cited by 556 · see citing works
Xu, Q., Bernardo, A., Walker, D., Kanegawa, T., Mahley, R. W., & Huang, Y. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5476-05.2006 · Cited by 524 · see citing works
Central Nervous System Lipoproteins: ApoE and Regulation of Cholesterol Metabolism
Mahley, R. W. (2016) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.116.307023 · Cited by 516 · see citing works
Sultana, R., Perluigi, M., & Butterfield, D. A. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.09.027 · Cited by 478 · see citing works
Schönfeld, P., & Reiser, G. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.128 · Cited by 457 · see citing works
Elusive roles for reactive astrocytes in neurodegenerative diseases
Ben Haim, L., Carrillo-de Sauvage, M.-A., Ceyzériat, K., & Escartin, C. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00278 · Cited by 453 · see citing works
Hipposeq: a comprehensive RNA-seq database of gene expression in hippocampal principal neurons
Cembrowski, M. S., Wang, L., Sugino, K., Shields, B. C., & Spruston, N. (2016) · eLife · doi:10.7554/elife.14997 · Cited by 422 · see citing works
Guo, Y., Cordes, K. R., Farese, R. V., & Walther, T. C. (2009) · Journal of Cell Science · doi:10.1242/jcs.037630 · Cited by 402 · see citing works
The role of astroglia in neuroprotection
Bélanger, M., & Magistretti, P. J. (2009) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2009.11.3/mbelanger · Cited by 396 · see citing works
Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism
Yellen, G. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201803152 · Cited by 371 · see citing works
Transmembrane molecular pump activity of Niemann-Pick C1 protein.
Davies, J. P., Chen, F.-N. W., & Ioannou, Y. (2000) · Science · doi:10.1126/science.290.5500.2295 · Cited by 346 · see citing works
Oxidized Low-Density Lipoprotein
Parthasarathy, S., Raghavamenon, A. C., Garelnabi, M., & Santanam, N. (2009) · Methods in molecular biology · doi:10.1007/978-1-60327-029-8_24 · Cited by 332 · see citing works
Ren, Z., Iliff, J. J., Yang, L., Yang, J., Chen, X., Chen, M. J., Giese, R. N., Wang, B., Shi, X., & Nedergaard, M. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.30 · Cited by 314 · see citing works
Redmann, M., Benavides, G. A., Berryhill, T. F., Wani, W. Y., Ouyang, X., Johnson, M. S., Ravi, S., Barnes, S., Darley-Usmar, V. M., & Zhang, J. (2016) · Redox Biology · doi:10.1016/j.redox.2016.11.004 · Cited by 257 · see citing works
ATP Excites Interneurons and Astrocytes to Increase Synaptic Inhibition in Neuronal Networks
Bowser, D. N., & Khakh, B. S. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2660-04.2004 · Cited by 241 · see citing works
Rong, X., Wang, B., Dunham, M. M., Hedde, P. N., Wong, J. S., Gratton, E., Young, S. G., Ford, D. A., & Tontonoz, P. (2015) · eLife · doi:10.7554/elife.06557 · Cited by 228 · see citing works
A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics
Nguyen, D., Alavi, M. V., Kim, K., Kang, T. H., Scott, R. T., Noh, Y. H., Lindsey, J. D., Wissinger, B., Ellisman, M. H., Weinreb, R. N., et al. (2011) · Cell Death and Disease · doi:10.1038/cddis.2011.117 · Cited by 226 · see citing works
Kim, W. S., Rahmanto, A. S., Kamili, A., Rye, K.-A., Guillemin, G. J., Gelissen, I. C., Jessup, W., Hill, A. F., & Garner, B. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607831200 · Cited by 191 · see citing works
Farr, T. D., & Whishaw, I. Q. (2002) · Stroke · doi:10.1161/01.str.0000020714.48349.4e · Cited by 161 · see citing works
DeMattos, R. B., Curtiss, L. K., & Williams, D. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.7.4206 · Cited by 123 · see citing works
Zhang, L., Song, J., Cavigiolio, G., Ishida, B. Y., Zhang, S., Kane, J. P., Weisgraber, K. H., Oda, M. N., Rye, K.-A., Pownall, H. J., et al. (2010) · Journal of Lipid Research · doi:10.1194/jlr.d010959 · Cited by 123 · see citing works
Zeng, Y., Tao, N., Chung, K.-N., Heuser, J. E., & Lublin, D. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307722200 · Cited by 122 · see citing works
Increased Expression of Neuronal Apolipoprotein E in Human Brain With Cerebral Infarction
Aoki, K., Uchihara, T., Sanjo, N., Nakamura, A., Ikeda, K., Tsuchiya, K., & Wakayama, Y. (2003) · Stroke · doi:10.1161/01.str.0000064320.73388.c6 · Cited by 108 · see citing works
Altered Lipid Droplet Dynamics in Hepatocytes Lacking Triacylglycerol Hydrolase Expression
Wang, H., Wei, E., Quiroga, A. D., Sun, X., Touret, N., & Lehner, R. S. (2010) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-05-0364 · Cited by 101 · see citing works
Schönfeld, P., & Reiser, G. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.03.018 · Cited by 99 · see citing works
Neuronal nicotinic acetylcholine receptor expression by O2A/oligodendrocyte progenitor cells
Rogers, S. W., Gregori, N. Z., Carlson, N. G., Gahring, L. C., & Noble, M. (2001) · Glia · doi:10.1002/1098-1136(20010315)33:4 · Cited by 94 · see citing works
Parihar, M. S., & Hemnani, T. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-003-0069-8 · Cited by 89 · see citing works
Haba, K., Ogawa, N., Mizukawa, K., & Mori, A. (1991) · Brain Research · doi:10.1016/0006-8993(91)90497-j · Cited by 87 · see citing works
NMDA Receptors in Glial Cells: Pending Questions
Džamba, D., Honsa, P., & Anděrová, M. (2013) · Current Neuropharmacology · doi:10.2174/1570159x11311030002 · Cited by 81 · see citing works
Buttini, M., Masliah, E., Yu, G.-Q., Palop, J. J., Chang, S., Bernardo, A., Lin, C., Wyss-Coray, T., Huang, Y., & Mucke, L. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.090973 · Cited by 80 · see citing works
Alaverdashvili, M., Moon, S.-K., Beckman, C., Virag, A., & Whishaw, I. Q. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.09.015 · Cited by 39 · see citing works
Karl, J. M., Alaverdashvili, M., Cross, A. R., & Whishaw, I. Q. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.06.054 · Cited by 24 · see citing works
Apolipoprotein E particle size is increased in Alzheimer's disease
Nelson, T. J., & Sen, A. (2018) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.10.005 · Cited by 16 · see citing works
Author response: Enhanced FIB-SEM systems for large-volume 3D imaging
Xu, C. S., Hayworth, K. J., Lu, Z., Grob, P., Hassan, A. M., García‐Cerdán, J. G., Niyogi, K., Nogales, E., Weinberg, R. J., & Hess, H. F. (2017) · eLife · doi:10.7554/elife.25916.033 · Cited by 7 · see citing works
Self-citationRong, X., Wang, B., Dunham, M. M., Hedde, P. N., Wong, J. S., Gratton, E., Young, S. G., Ford, D. A., & Tontonoz, P. (2015) · eLife · doi:10.7554/elife.06557.026 · Cited by 6 · see citing works
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3 of the 72 references couldn’t be matched to a known paper.
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Sorted by citations
Reactive astrocyte nomenclature, definitions, and future directions
Escartin, C., Galea, E., Lakatos, A., O’Callaghan, J. P., Petzold, G. C., Serrano-Pozo, A., Steinhäuser, C., Volterra, A., Carmignoto, G., Agarwal, A., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00783-4 · Cited by 2,533 · see citing works
Zhou, Y., Song, W. M., Andhey, P. S., Swain, A., Levy, T., Miller, K. R., Poliani, P. L., Cominelli, M., Grover, S., Gilfillan, S., et al. (2020) · Nature Medicine · doi:10.1038/s41591-019-0695-9 · Cited by 1,150 · see citing works
Lipid droplet biogenesis and functions in health and disease
Zadoorian, A., Du, X., & Yang, H. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00845-0 · Cited by 617 · see citing works
Neurotoxic reactive astrocytes induce cell death via saturated lipids
Guttenplan, K. A., Weigel, M. K., Prakash, P., Wijewardhane, P. R., Hasel, P., Rufen-Blanchette, U., Münch, A. E., Blum, J. A., Fine, J., Neal, M. C., et al. (2021) · Nature · doi:10.1038/s41586-021-03960-y · Cited by 578 · see citing works
APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia
Haney, M. S., Pálovics, R., Munson, C. N., Long, C., Johansson, P. K., Yip, O., Dong, W., Rawat, E., West, E., Schlachetzki, J. C. M., et al. (2024) · Nature · doi:10.1038/s41586-024-07185-7 · Cited by 536 · see citing works
“For example, cell culture models have demonstrated that hyperactive neurons can release APOE -associated fatty acids which are taken up by astrocytes and buffer lipotoxic stress 35 .”
Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity
Yoon, H., Shaw, J. L., Haigis, M. C., & Greka, A. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.08.027 · Cited by 521 · see citing works
Yin, F. (2023) · The FEBS Journal · doi:10.1111/febs.16344 · Cited by 441 · 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
Energy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 438 · see citing works
Self-citationImmune cell regulation of glia during CNS injury and disease
Greenhalgh, A. D., David, S., & Bennett, F. C. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0263-9 · Cited by 398 · see citing works
Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism
Poitelon, Y., Kopec, A. M., & Belin, S. (2020) · Cells · doi:10.3390/cells9040812 · Cited by 394 · see citing works
ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism
Qi, G., Mi, Y., Shi, X., Gu, H., Brinton, R. D., & Yin, F. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108572 · Cited by 379 · see citing works
Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity
Victor, M. B., Leary, N., Luna, X., Meharena, H. S., Scannail, A. N., Bozzelli, P. L., Samaan, G., Murdock, M. H., von Maydell, D., Effenberger, A. H., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.07.005 · Cited by 316 · see citing works
Lipid metabolism and lipid signals in aging and longevity
Mutlu, A. S., Duffy, J. D., & Wang, M. C. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.03.034 · Cited by 311 · see citing works
Apolipoprotein E in lipid metabolism and neurodegenerative disease
Yang, L. G., March, Z. M., Stephenson, R. A., & Narayan, P. S. (2023) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2023.05.002 · Cited by 286 · see citing works
Lipid droplets and cellular lipid flux
Mathiowetz, A. J., & Olzmann, J. A. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01364-4 · Cited by 299 · see citing works
Lipid droplets in the nervous system
Ralhan, I., Chang, C.-L., Lippincott-Schwartz, J., & Ioannou, M. S. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202102136 · Cited by 281 · see citing works
Self-citationFernández-Calle, R., Konings, S. C., Frontiñán-Rubio, J., García-Revilla, J., Camprubí-Ferrer, L., Svensson, M., Martinson, I., Boza-Serrano, A., Venero, J. L., Nielsen, H. M., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00566-4 · Cited by 278 · see citing works
Lipid droplets in neurodegenerative disorders
Farmer, B. C., Walsh, A. E., Kluemper, J. C., & Johnson, L. A. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00742 · Cited by 270 · see citing works
Andersen, J. V., Schousboe, A., & Verkhratsky, A. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102331 · Cited by 259 · see citing works
iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer
Park, D. S., Kozaki, T., Tiwari, S. K., Moreira, M., Khalilnezhad, A., Torta, F. T., Olivié, N., Thiam, C. H., Liani, O., Silvin, A., et al. (2023) · Nature · doi:10.1038/s41586-023-06713-1 · Cited by 237 · see citing works
Strategies to reduce the risks of mRNA drug and vaccine toxicity
Bitounis, D., Jacquinet, E., Rogers, M. A., & Amiji, M. M. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00859-3 · Cited by 237 · see citing works
Cholesterol and Alzheimer’s Disease; From Risk Genes to Pathological Effects
Feringa, F. M., & van der Kant, R. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.690372 · Cited by 226 · see citing works
Lipid-accumulated reactive astrocytes promote disease progression in epilepsy
Chen, Z.-P., Wang, S., Zhao, X., Fang, W., Wang, Z., Ye, H., Wang, M.-J., Ke, L., Huang, T., Lv, P., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01288-6 · Cited by 214 · see citing works
The “Neuro-Glial-Vascular” Unit: The Role of Glia in Neurovascular Unit Formation and Dysfunction
Kugler, E., Greenwood, J., & MacDonald, R. B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.732820 · Cited by 215 · see citing works
Early Alzheimer’s disease pathology in human cortex involves transient cell states
Gazestani, V., Kamath, T., Nadaf, N. M., Dougalis, A., Burris, S. J., Rooney, B., Junkkari, A., Vanderburg, C., Pelkonen, A., Gomez-Budia, M., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.005 · Cited by 209 · see citing works
Ni, X.-C., Wang, H.-F., Cai, Y.-Y., Yang, D., Alolga, R. N., Liu, B., Li, J., & Huang, F.-Q. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102363 · Cited by 203 · see citing works
Rose, J., Brian, C., Pappa, A., Panayiotidis, M. I., & Franco, R. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.536682 · Cited by 196 · see citing works
Mitochondrial heterogeneity and homeostasis through the lens of a neuron
Pekkurnaz, G., & Wang, X. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00594-w · Cited by 195 · see citing works
Fatty acid oxidation organizes mitochondrial supercomplexes to sustain astrocytic ROS and cognition
Morant-Ferrando, B., Jiménez-Blasco, D., Alonso-Batan, P., Agulla, J., Lapresa, R., García-Rodríguez, D., Yunta-Sanchez, S., López-Fabuel, I., Fernández, E., Carmeliet, P., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00835-6 · Cited by 193 · see citing works
Lipid Metabolism Crosstalk in the Brain: Glia and Neurons
Barber, C. N., & Raben, D. M. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00212 · Cited by 188 · see citing works
The neuropathobiology of multiple sclerosis
Woo, M. S., Engler, J. B., & Friese, M. A. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-024-00823-z · Cited by 194 · see citing works
TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination
Gouna, G., Klose, C., Bosch-Queralt, M., Liu, L., Gokce, O., Schifferer, M., Cantuti-Castelvetri, L., & Simons, M. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20210227 · Cited by 186 · see citing works
Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases
Yang, D., Wang, X., Zhang, L., Fang, Y., Zheng, Q., Liu, X., Yu, W., Chen, S., Ying, J., & Hua, F. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00828-0 · Cited by 179 · see citing works
A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility
Sheu, S.-H., Upadhyayula, S., Dupuy, V., Pang, S., Deng, F., Wan, J., Walpita, D., Pasolli, H. A., Houser, J., Sanchez-Martinez, S., et al. (2022) · Cell · doi:10.1016/j.cell.2022.07.026 · Cited by 162 · see citing works
Self-citationMoulton, M. J., Barish, S., Ralhan, I., Chang, J., Goodman, L. D., Harland, J. G., Marcogliese, P. C., Johansson, J. O., Ioannou, M. S., & Bellen, H. J. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2112095118 · Cited by 180 · see citing works
Self-citationAstrocyte-oligodendrocyte interaction regulates central nervous system regeneration
Molina-Gonzalez, I., Holloway, R. K., Jiwaji, Z., Dando, O., Kent, S. A., Emelianova, K., Lloyd, A. F., Forbes, L. H., Mahmood, A., Skripuletz, T., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39046-8 · Cited by 176 · see citing works
“Next, using a previously established in vitro method to track direct cholesteroltransferbetweencelltypes 37 ,weloadedastrocyteswiththe fl uorescent cholesterol analogue Bodipy-FL-C12 for 6h (Fig.”
Lipid droplets and polyunsaturated fatty acid trafficking: Balancing life and death
Danielli, M., Perne, L., Jarc Jovičić, E., & Petan, T. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1104725 · Cited by 180 · see citing works
Fatty acid metabolism in the progression and resolution of CNS disorders
Bogie, J. F. J., Haidar, M., Kooij, G., & Hendriks, J. J. A. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.01.004 · Cited by 167 · see citing works
Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK
Li, Y., Munoz-Mayorga, D., Nie, Y., Kang, N., Tao, Y., Lagerwall, J., Pernaci, C., Curtin, G., Coufal, N. G., Mertens, J., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.03.014 · Cited by 160 · see citing works
Microglia and lipids: how metabolism controls brain innate immunity
Chausse, B., Kakimoto, P. A., & Kann, O. (2021) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2020.08.001 · Cited by 181 · see citing works
Alterations in lipid metabolism of spinal cord linked to amyotrophic lateral sclerosis
Chaves‐Filho, A. B., Pinto, I. F. D., Dantas, L. S., Xavier, A. M., Inague, A., de Faria, R. L., de Medeiros, M. H. G., Glezer, I., Yoshinaga, M. Y., & Miyamoto, S. (2019) · Scientific Reports · doi:10.1038/s41598-019-48059-7 · Cited by 158 · see citing works
Sun, Y., Zhang, H., Zhang, X., Wang, W., Chen, Y., Cai, Z., Wang, Q., Wang, J., & Shi, Y. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102690 · Cited by 151 · see citing works
Andersen, J. V., & Schousboe, A. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15811 · Cited by 152 · see citing works
The Glutamate/ GABA ‐Glutamine Cycle: Insights, Updates, and Advances
Andersen, J. V. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70029 · Cited by 156 · see citing works
Insights into Alzheimer’s disease from single-cell genomic approaches
Murdock, M. H., & Tsai, L.-H. (2023) · Nature Neuroscience · doi:10.1038/s41593-022-01222-2 · Cited by 148 · see citing works
Lipid droplets and lipid mediators in viral infection and immunity
Monson, E. A., Trenerry, A. M., Laws, J., Mackenzie, J. M., & Helbig, K. J. (2020) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaa066 · Cited by 145 · see citing works
Papsdorf, K., Miklas, J. W., Hosseini, A., Cabruja, M., Morrow, C. S., Savini, M., Yu, Y., Silva-García, C. G., Haseley, N. R., Murphy, L., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01136-6 · Cited by 145 · see citing works
A neuron–glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis
Haynes, P. R., Pyfrom, E. S., Li, Y., Stein, C., Cuddapah, V. A., Jacobs, J. A., Yue, Z., & Sehgal, A. (2024) · Nature Neuroscience · doi:10.1038/s41593-023-01568-1 · Cited by 146 · see citing works
Kelly, W., Duque, A. E. D., Michalek, J. E., Konkel, B., Caflisch, L., Chen, Y., Pathuri, S. C., Madhusudanannair-Kunnuparampil, V., Floyd, J., & Brenner, A. J. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-2807 · Cited by 142 · see citing works
Glia fuel neurons with locally synthesized ketone bodies to sustain memory under starvation
Silva, B., Mantha, O. L., Schor, J., Pascual, A., Plaçais, P.-Y., Pavlowsky, A., & Préat, T. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00528-6 · Cited by 138 · see citing works
Astrocytes in stress accumulate lipid droplets
Smolič, T., Verdev, P. T., Horvat, A., Černe, U., Vasle, A. H., Tratnjek, L., Kreft, M. E., Scholz, N., Matis, M., Petan, T., et al. (2021) · Glia · doi:10.1002/glia.23978 · Cited by 136 · see citing works
Oligodendroglial fatty acid metabolism as a central nervous system energy reserve
Asadollahi, E., Trevisiol, A., Saab, A. S., Looser, Z. J., Dibaj, P., Ebrahimi, R., Kusch, K., Ruhwedel, T., Möbius, W., Jahn, O., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01749-6 · Cited by 130 · see citing works
Chen, M., Gao, Q., Ning, H., Chen, K., Gao, Y., Yu, M., Liu, C., Zhou, W., Pan, J., Wei, L., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.06.020 · Cited by 137 · see citing works
Lipidome atlas of the adult human brain
Osetrova, M., Tkachev, A., Mair, W., Larraz, P. G., Efimova, O., Kurochkin, I., Stekolshchikova, E., Anikanov, N. A., Foo, J. C., Cazenave‐Gassiot, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48734-y · Cited by 129 · see citing works
Lipid droplet availability affects neural stem/progenitor cell metabolism and proliferation
Ramosaj, M., Madsen, S., Maillard, V., Scandella, V., Sudria-Lopez, D., Yuizumi, N., Telley, L., & Knobloch, M. (2021) · Nature Communications · doi:10.1038/s41467-021-27365-7 · Cited by 122 · see citing works
Astrocyte-Neuron Metabolic Crosstalk in Neurodegeneration: A Mitochondrial Perspective
Mulica, P., Grünewald, A., & Pereira, S. L. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.668517 · Cited by 121 · see citing works
Jacquet, A. D. R., Alpaugh, M., Denis, H. L., Tancredi, J. L., Boutin, M., Decaestecker, J., Beauparlant, C., Herrmann, L., Saint-Pierre, M., Parent, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39038-8 · Cited by 114 · see citing works
Lipid metabolism in astrocytic structure and function
Lee, J. A., Hall, B., Allsop, J., Alqarni, R., & Allen, S. P. (2021) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2020.07.017 · Cited by 116 · 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
Brekk, O. R., Honey, J. R., Lee, S., Hallett, P. J., & Ole Isacson, A. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003021117 · Cited by 115 · see citing works
Metabolic changes favor the activity and heterogeneity of reactive astrocytes
Xiong, X., Tang, Y., & Yang, Q. (2022) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2022.03.001 · Cited by 109 · see citing works
Protein Quality Control and Lipid Droplet Metabolism
Roberts, M. A., & Olzmann, J. A. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-031320-101827 · Cited by 107 · see citing works
Brain energy metabolism: A roadmap for future research
Rae, C. D., Baur, J. A., Borges, K., Dienel, G. A., Díaz‐García, C. M., Douglass, S. R., Drew, K. L., Duarte, J. M. N., Durán, J., Kann, O., et al. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16032 · Cited by 109 · see citing works
Lipid and immune abnormalities causing age-dependent neurodegeneration and Parkinson’s disease
Hallett, P. J., Engelender, S., & Ole Isacson, A. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1532-2 · Cited by 105 · see citing works
Han, X., Zhao, S., Song, H., Xu, T., Fang, Q., Hu, G., & Sun, L. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101911 · Cited by 105 · see citing works
Prakash, P., Manchanda, P., Paouri, E., Bisht, K., Sharma, K., Rajpoot, J., Wendt, V., Hossain, A., Wijewardhane, P. R., Randolph, C. E., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.04.029 · Cited by 104 · see citing works
Kaji, S., Berghoff, S. A., Spieth, L., Schlaphoff, L., Sasmita, A. O., Vitale, S., Büschgens, L., Kedia, S., Zirngibl, M., Nazarenko, T., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.09.014 · Cited by 104 · see citing works
The cell biology of APOE in the brain
Windham, I. A., & Cohen, S. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.09.004 · Cited by 103 · see citing works
Diversity of satellite glia in sympathetic and sensory ganglia
Mapps, A. A., Thomsen, M. B., Boehm, E. D., Zhao, H., Hattar, S. S., & Kuruvilla, R. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110328 · Cited by 103 · see citing works
Afridi, R., Kim, J., Rahman, M. H., & Suk, K. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00020 · Cited by 98 · see citing works
Focusing on mitochondria in the brain: from biology to therapeutics
Song, N., Mei, S., Wang, X.-X., Hu, G., & Lu, M. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00409-w · Cited by 102 · see citing works
APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size
Windham, I. A., Powers, A. E., Ragusa, J. V., Wallace, E. D., Zanellati, M. C., Williams, V. H., Wagner, C. H., White, K. K., & Cohen, S. (2024) · Journal of Cell Biology · doi:10.1083/jcb.202305003 · Cited by 96 · see citing works
Mitochondrial dysfunction in astrocytes: A role in Parkinson’s disease?
Bantle, C. M., Hirst, W. D., Weihofen, A., & Shlevkov, E. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.608026 · Cited by 95 · see citing works
Kim, O. Y., & Song, J. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122356 · Cited by 96 · see citing works
Lipid droplets and fatty acid‐induced lipotoxicity: in a nutshell
Obaseki, E., Adebayo, D., Bandyopadhyay, S., & Hariri, H. H. (2024) · FEBS Letters · doi:10.1002/1873-3468.14808 · Cited by 92 · see citing works
Guo, J. L., Braun, D., Fitzgerald, G. A., Hsieh, Y.-T., Rougé, L., Litvinchuk, A., Steffek, M., Propson, N. E., Heffner, C. M., Discenza, C., et al. (2025) · Cell · doi:10.1016/j.cell.2024.10.027 · Cited by 91 · see citing works
“62 Additionally, APOE4 expression in human iMg was shown to induce secretion of lipids, which promoted tau phosphorylation in neurons.”
Ceramide accumulation induces mitophagy and impairs β-oxidation in PINK1 deficiency
Vos, M. H., Dulovic‐Mahlow, M., Mandik, F., Frese, L., Kanana, Y., Diaw, S. H., Depperschmidt, J., Böhm, C., Rohr, J., Lohnau, T., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2025347118 · Cited by 91 · see citing works
Lipid Droplet–Mitochondria Contacts in Health and Disease
Fan, H., & Tan, Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25136878 · Cited by 90 · see citing works
Andersen, J. V., Westi, E. W., Jakobsen, E., Urruticoechea, N., Borges, K., & Aldana, B. I. (2021) · Molecular Brain · doi:10.1186/s13041-021-00842-2 · Cited by 89 · see citing works
Jacquet, A. D. R., Tancredi, J. L., Lemire, A. L., DeSantis, M. C., Li, W., & O’Shea, E. K. (2021) · eLife · doi:10.7554/elife.73062 · Cited by 89 · see citing works
Isoform- and cell-state-specific lipidation of ApoE in astrocytes
Lindner, K., Beckenbauer, K., van Ek, L. C., Titeca, K., de Leeuw, S. M., Awwad, K., Hanke, F., Korepanova, A. V., Rybin, V., van der Kam, E. L., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110435 · Cited by 84 · see citing works
Alarcón-Gil, J., Sierra‐Magro, A., Morales-Garcia, J. A., Sanz-SanCristóbal, M., Alonso‐Gil, S., Cortés‐Canteli, M., Niso‐Santano, M., Martínez-Chacón, G., Fuentes, J. M., Santos, Á., et al. (2022) · Cells · doi:10.3390/cells11152297 · Cited by 87 · see citing works
Apolipoprotein E4 and meningeal lymphatics in Alzheimer disease: a conceptual framework
Mentis, A. A., Dardiotis, E., & Chrousos, G. P. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0731-7 · Cited by 82 · see citing works
Apolipoprotein E in Alzheimer’s disease: molecular insights and therapeutic opportunities
Belaidi, A. A., Bush, A. I., & Ayton, S. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00843-y · Cited by 91 · see citing works
Lipid metabolism, remodelling and intercellular transfer in the CNS
Vanherle, S., Loix, M., Miron, V. E., Hendriks, J. J. A., & Bogie, J. F. J. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00908-3 · Cited by 90 · see citing works
Recent insights on astrocyte mechanisms in CNS homeostasis, pathology, and repair
Hart, C. G., & Karimi‐Abdolrezaee, S. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24922 · Cited by 85 · see citing works
Neurogenetic basis for circadian regulation of metabolism by the hypothalamusPreprint
Cedernaes, J., Waldeck, N. J., & Bass, J. T. (2019) · Genes & Development · doi:10.1101/gad.328633.119 · Cited by 84 · see citing works
Hypothalamic inflammation in metabolic disorders and aging
Bhusal, A., Rahman, M. H., & Suk, K. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04019-x · Cited by 79 · see citing works
Velebit, J., Horvat, A., Smolič, T., Mihevc, S. P., Rogelj, B., Zorec, R., & Vardjan, N. (2020) · Scientific Reports · doi:10.1038/s41598-020-62864-5 · Cited by 78 · see citing works
Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward autoactivation loop in mice
Varela, L., Stutz, B., Song, J. E., Kim, J. G., Liu, Z.-W., Gao, X., & Horváth, T. L. (2021) · Journal of Clinical Investigation · doi:10.1172/jci144239 · Cited by 75 · see citing works
Self-citationNeuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice
Berghoff, S. A., Spieth, L., Sun, T., Hosang, L., Depp, C., Sasmita, A. O., Vasileva, M. H., Scholz, P., Zhao, Y., Krueger‐Burg, D., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109889 · Cited by 75 · see citing works
Takahashi, S. (2020) · Neuropathology · doi:10.1111/neup.12639 · Cited by 75 · see citing works
Al‐Dalahmah, O., Argenziano, M., Kannan, A., Mahajan, A., Furnari, J. L., Paryani, F., Boyett, D. M., Save, A., Humala, N., Khan, F., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38186-1 · Cited by 74 · see citing works
Remembering your A, B, C's: Alzheimer's disease and ABCA1
Lewandowski, C. T., Laham, M. S., & Thatcher, G. R. J. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.01.011 · Cited by 76 · see citing works
Nakajima, S., Gotoh, M., Fukasawa, K., Murakami‐Murofushi, K., & Kunugi, H. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146484 · Cited by 72 · see citing works
Wang, Y., Fu, A. K. Y., & Ip, N. Y. (2021) · FEBS Journal · doi:10.1111/febs.15878 · Cited by 71 · see citing works
How the brain fights fatty acids’ toxicity
Schönfeld, P., & Reiser, G. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.105050 · Cited by 70 · see citing works
Castellanos, D. B., Martín-Jiménez, C., Rojas-Rodríguez, F., Barreto, G., & Santos, J. G. (2021) · Frontiers in neuroendocrinology (Print) · doi:10.1016/j.yfrne.2021.100899 · Cited by 58 · see citing works
Girard, V., Jollivet, F., Knittelfelder, O. L., Celle, M., Arsac, J.-N., Chatelain, G., van den Brink, D. M., Baron, T., Shevchenko, A., Kühnlein, R. P., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009921 · Cited by 70 · see citing works
- Authors
- Ioannou, M. S., Jackson, J., Sheu, S.-H., Chang, C.-L., Weigel, A. V., Liu, H., Pasolli, H. A., Xu, C. S., Pang, S., Matthies, D., Hess, H. F., Lippincott-Schwartz, J., & Liu, Z.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of Alberta (CA)
- Corresponding author
- Ioannou, Maria S.
- Liu, Zhe
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 177
- Issue
- 6
- Pages
- 1522-1535.e14
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2946373463
- Cited by
- 760
- References
- 72
- Citations by year
- 2026: 129 · 2025: 150 · 2024: 133 · 2023: 117 · 2022: 74 · 2021: 92 · 2020: 47 · 2019: 15 · 2018: 1
- FWCI
- 23.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- fatty acid toxicity, lipid droplets, apolipoprotein E, mitochondrial beta-oxidation, fatty acid metabolism, neuronal hyperactivity, astrocytes, lipid metabolism, neuroprotection
- MeSH terms
- Animals, Apolipoproteins E, Astrocytes, Brain, Fatty Acids, Homeostasis, Male, Mice, Inbred C57BL, Mitochondria, Neurons, Oxidation-Reduction, Rats, Sprague-Dawley, Mice, Knockout, Lipid Metabolism, Mice, Rats, Lipid Droplets
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