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Synuclein activates microglia in a model of Parkinson's disease
Open accessAbstract
Parkinson's disease (PD) is the most common neurodegenerative movement disorder afflicting >500,000 patients in the United States alone. This age-related progressive disorder is typified by invariant loss of dopaminergic substantia nigra neurons (DAN), dystrophic neurites, the presence of alpha-synuclein (SYN) positive intracytoplasmic inclusions (Lewy bodies) in the remaining DAN, and activated microglia. As such, microglial activation and resultant increase in proinflammatory molecules have moved to the forefront of PD research as a potential pathobiologic mechanism of disease. Herein, we present data demonstrating early microglial activation in mice that over-express wild-type SYN, the release of SYN from a SYN overexpressing MN9D cell line, and dose-dependent SYN-mediated activation of primary microglial cultures with consequent increases in proinflammatory molecules. Furthermore, we provide evidence that the CD36 scavenger receptor and downstream kinases are involved in SYN-mediated microglial activation. Together, our data suggest an early role for SYN and inflammation in PD pathogenesis.
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“SR-B2 promotes α-synuclein–microglial interactions64 and senses misfolded mutant or oxidized SOD1 in diseased motor neurons or in the extracellular space, rendering these cells proinflammatory85.”
From Microglia in neurodegeneration (2018) · cites this paper as [64]
In the citing paper
“Microglia accumulate near α-synuclein deposits and become proinflammatory in a manner dependent on receptors that also bind Aβ, such as CD36 and TLR263–65.”
From Microglia in neurodegeneration (2018) · cites this paper as [64]
In the citing paper
“Microglia also phagocytose α-synuclein, the constituent protein of Lewy bodies in Parkinson’s and Lewy Body dementias, and become pro-inflammatory in the process, expressing cytokines (IL1β, IL6, TNFα), reactive oxygen species (ROS) and prostaglandin synthesising cyclooxygenase 2 (COX2) [24,25,26].”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [25]
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Lee, J., Tan, V. X., Lovejoy, D. B., Braidy, N., Rowe, D. B., Brew, B. J., & Guillemin, G. J. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.05.011 · Cited by 52
Potential Therapeutic Role of Carnitine and Acetylcarnitine in Neurological Disorders
Maldonado, C., Vázquez, M., & Fagiolino, P. L. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200212114038 · Cited by 49
Lack of Alpha-Synuclein Modulates Microglial Phenotype In Vitro
Austin, S. A., Rojanathammanee, L., Golovko, M. Y., Murphy, E. J., & Combs, C. K. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0439-9 · Cited by 51
“The consequence of these stimulations invariably demonstrate changes in microglial phenotype favoring a reactive state that includes a range of changes such as increased secretion of cytokines [46], increased proinflammatory protein levels [46, 50], increased adhesion”
BackgroundDAT and TH expression marks human Parkinson’s disease in peripheral immune cells
Gopinath, A., Mackie, P. M., Hashimi, B., Buchanan, A. M., Smith, A. R., Bouchard, R. S., Shaw, G., Badov, M., Saadatpour, L., Gittis, A. H., et al. (2022) · npj Parkinson s Disease · doi:10.1038/s41531-022-00333-8 · Cited by 47
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Genetic Defects and Pro-inflammatory Cytokines in Parkinson's Disease
Magnusen, A. F., Hatton, S. L., Rani, R., & Pandey, M. K. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.636139 · Cited by 47
Alpha Synuclein in Parkinson’s Disease
Kragh, C. L., Romero‐Ramos, M., Halliday, G. M., & Jensen, P. H. (2014) · Springer eBooks · doi:10.1007/978-1-4614-5836-4_14 · Cited by 48
CD36 – A novel molecular target in the neurovascular unit
Ioghen, O., Chițoiu, L., Gherghiceanu, M., Ceafalan, L. C., & Hinescu, M. E. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15147 · Cited by 47
“One study showed that alpha- synuclein activates microglia in a process that involves CD36, promoting a pro- inflammatory response early in the disease (Su et al., 2008).”
BackgroundAlpha-Synuclein and Microglia in Parkinson’s Disease: From Pathogenesis to Therapeutic Prospects
Eo, H., Kim, S., Jung, U. J., & Kim, S. R. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13237243 · Cited by 47
An emerging role for LRRK2 in the immune system
Dzamko, N. L., & Halliday, G. M. (2012) · Biochemical Society Transactions · doi:10.1042/bst20120119 · Cited by 45
“In particular, recent work has suggested that alpha-synuclein can induce the secretion of inflammatory cytokines [45] and even increase the expression of TLR’s [46].”
BackgroundKim, C., Ojo-Amaize, E., Spencer, B., Rockenstein, E., Mante, M., Desplats, P., Wrasidlo, W., Adame, A., Nchekwube, E., Oyemade, O., et al. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0455-9 · Cited by 45
“Previous studies have shown that exposure to various forms of recombinant α-synuclein induces microglia activation [25, 33–35].”
BackgroundMolecular events underlying the cell‐to‐cell transmission of α‐synuclein
Choi, Y. R., Park, S., & Park, S. M. (2020) · FEBS Journal · doi:10.1111/febs.15674 · Cited by 47
Future directions for immune modulation in neurodegenerative disorders: focus on Parkinson’s disease
Maguire‐Zeiss, K. A., & Federoff, H. J. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0431-6 · Cited by 46
Self-citationAquaporin 4: A key player in Parkinson's disease
Tamtaji, O. R., Behnam, M., Pourattar, M. A., Jafarpour, H., & Asemi, Z. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28871 · Cited by 44
“In addition, many studies have indicated that α‐synuclein activates microglia in PD (Su et al., 2008).”
BackgroundPradhan, S., & Andreasson, K. I. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.12.008 · Cited by 43
Immune-mediated processes in neurodegeneration: where do we stand?
Fakhoury, M. (2016) · Journal of Neurology · doi:10.1007/s00415-016-8052-0 · Cited by 43
“Activation of microglia in transgenic mice triggers a cascade of pro-inflammatory events in the substantia nigra, which leads to the up-regulation of cytokines, enzymes, and mediators of reactive oxygen species [127, 128].”
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Galindo, A. N., Rubio, D. A. F., & Hettiaratchi, M. H. (2024) · Materials Advances · doi:10.1039/d3ma00736g · Cited by 49
“86,87 Prolonged activity of reactive astrocytes and microglia has been identified as a hallmark of several neurodegenerative diseases, including stroke, multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease.”
BackgroundiPSC-Derived Microglia as a Model to Study Inflammation in Idiopathic Parkinson’s Disease
Badanjak, K., Mulica, P., Smajić, S., Delcambre, S., Tranchevent, L.-C., Diederich, N. J., Rauen, T., Schwamborn, J. C., Glaab, E., Cowley, S. A., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.740758 · Cited by 45
Kim, J.-H., Jou, I., & Joe, E.-H. (2014) · Experimental Neurobiology · doi:10.5607/en.2014.23.2.148 · Cited by 43
“In this context, we and others have reported that both loss-of-function mutants of PD genes (PINK and DJ-1) and gain-of-function mutants of PD genes (a-synuclein and LRRK2) enhance inflammatory responses [9, 36-38].”
BackgroundVoltage-gated calcium channels and Parkinson's disease
Hurley, M. J., & Dexter, D. T. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.11.006 · Cited by 46
α-Synuclein: A therapeutic target for Parkinson’s disease?
Maguire‐Zeiss, K. A. (2008) · Pharmacological Research · doi:10.1016/j.phrs.2008.09.006 · Cited by 44
“imagine utilizing a similar approach in PD since in vitro and in vivo SYN overexpression models demonstrate that misfolded conformers exist and are toxic, SYN can be released from cells, microglial activation occurs as early as one month of age, and SYN directly activates microglia partially through the CD36 pattern r…”
BackgroundSelf-citationTranslation Imaging in Parkinson’s Disease: Focus on Neuroinflammation
Belloli, S., Morari, M., Murtaj, V., Valtorta, S., Moresco, R. M., & Gilardi, M. C. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00152 · Cited by 43
Zhang, J., Zhao, M., Yan, R., Liu, J., Maddila, S. C., Junn, E., & Mouradian, M. M. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01130-6 · Cited by 42
“α-Syn is known to activate microglia in various experimental paradigms including human microglial cells isolated from surgically resected human temporal lobe tissue, mouse primary microglial cultures, and in mice overexpressing α-syn [36, 37].”
BackgroundGuenoun, D., Blaise, N., Sellam, A., Roupret‐Serzec, J., Jacquens, A., Steenwinckel, J. V., Gressèns, P., & Bokobza, C. (2024) · Glia · doi:10.1002/glia.24664 · Cited by 41
“…diseases (86) such as multiple sclerosis (Perry, Nicoll, and Holmes 2010), Alzheimer's disease (AD) (Baik et al. 2019; Olah et al. 2020), Parkinson's disease (Su et al. 2008; Kim et al. 2013; Croisier et al. 2005) or Huntington's disease (Tai et al. 2007; Sapp et al. 2001; Pavese et al. 2006).”
Alieva, A. K., Shadrina, M. I., Filatova, E. V., Karabanov, A. V., Illarioshkin, S. N., Limborska, S. A., & Slominsky, P. A. (2014) · BioMed Research International · doi:10.1155/2014/718732 · Cited by 41
“Experiments performed in vitro showed that misfolded synuclein activates microglia, which in turn leads to the secretion of cytokines, such asTNFα [29] and IL-1β [30], and to the production of ROS, which damage DA neurons [31].”
BackgroundModeling Parkinson’s Disease Using Patient-specific Induced Pluripotent Stem Cells
Li, H., Jiang, H., Zhang, B., & Feng, J. (2018) · Journal of Parkinson s Disease · doi:10.3233/jpd-181353 · Cited by 44
“impact neurons but also directly activate and induce 553 TNF- release from primary microglial cultures 554 [127].”
BackgroundNoninvasive vagus nerve stimulation in Parkinson’s disease: current status and future prospects
Sigurdsson, H. P., Raw, R. K., Hunter, H., Baker, M. R., Taylor, J., Rochester, L., & Yarnall, A. J. (2021) · Expert Review of Medical Devices · doi:10.1080/17434440.2021.1969913 · Cited by 44
“In PD, DMNV neurons are highly susceptible to neurodegeneration, and contain phosphorylated α-synuclein [40] leading to neuroinflammatory processes [94].”
BackgroundTowards translational therapies for multiple system atrophy
Kuzdas-Wood, D., Stefanova, N., Jellinger, K. A., Seppi, K., Schlossmacher, M. G., Poewe, W. H., & Wenning, G. K. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.02.007 · Cited by 39
(Re)building the nervous system: A review of neuron–glia interactions from development to disease
Demmings, M. D., Chagas, L. D. S., Traetta, M. E., Rodrigues, R. S., Acutain, M. F., Barykin, E. P., Datusalia, A. K., German‐Castelan, L., Mattera, V. S., Mazengenya, P., et al. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16258 · Cited by 44
“Similarly, activated microglia have also been described in PD post-mortem brains and mice expressing α - synuclein (McGeer et al., 1988; Su et al., 2008 ).”
Biomarkers and the Role of α-Synuclein in Parkinson’s Disease
Du, T., Wang, L., Liu, W., Zhu, G., Chen, Y., & Zhang, J. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.645996 · Cited by 41
Extracellular alpha-synuclein: Sensors, receptors, and responses
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Regulation of Weibel-Palade Body Exocytosis by α-Synuclein in Endothelial Cells
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Wilkaniec, A., Strosznajder, J. B., & Adamczyk, A. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2013.02.004 · Cited by 37
“Additionally, it was shown that ASN could partially influence the microglial function by binding to and activating the cell surface CD36 scavenger receptor (Su et al., 2008) or the Mac-1 receptor (Zhang et al., 2007).”
Transglutaminase 2 exacerbates α‐synuclein toxicity in mice and yeast
Jasutkar, H. G., Woo, J., Lee, K., Im, J., Masliah, E., Junn, E., & Mouradian, M. M. (2014) · The FASEB Journal · doi:10.1096/fj.14-251413 · Cited by 36
Neuroinflammatory responses in Parkinson’s disease: relevance of Ibuprofen in therapeutics
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“exacerbated by the presence of misfolded and/or aggregated disease-causing proteins [151–153].”
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Immune-related biomarkers for Parkinson's disease
Abdi, I. Y., Ghanem, S. S., & El‐Agnaf, O. M. A. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105771 · Cited by 38
Neurodegeneration and inflammation crosstalk: Therapeutic targets and perspectives
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“anism [23–27].”
Anti-Inflammatory and Neuroprotective Effects of PGE2 EP4 Signaling in Models of Parkinson’s Disease
Pradhan, S., Salinas, K. J., Garduno, A. C., Johansson, J. U., Wang, Q., Manning-Bog, A., & Andreasson, K. I. (2016) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-016-9713-6 · Cited by 36
Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies
Kwon, S., Iba, M., Masliah, E., & Kim, C. (2019) · Experimental Neurobiology · doi:10.5607/en.2019.28.5.547 · Cited by 35
“Neurons release various forms of α-syn, including monomers, oligomers, and high molecular weight aggregates [31-34].”
BackgroundParkinson Disease: Translating Insights from Molecular Mechanisms to Neuroprotection
Pirooznia, S. K., Rosenthal, L. S., Dawson, V. L., & Dawson, T. M. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000189 · Cited by 36
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“The neuropathological hallmarks of PD are characterized by the presence of eosinophilic, intracytoplasmic, * Carmela Conte carmela.conte@unipg.it 1 Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy 2 Department of Experimental Medicine, University of Perugia, Perugia, Italy proteinaceo…”
BackgroundJęśko, H. M., Lenkiewicz, A. M., Wilkaniec, A., & Adamczyk, A. (2019) · Acta Neurobiologiae Experimentalis · doi:10.21307/ane-2019-026 · Cited by 34
“Indeed, α‑syn has been shown to act as an inflammatory stimulator that modulates microglial expression of proinflammato‑ ry cytokines, such as tumor necrosis factor α (TNF‑α) and inducible NOS (iNOS) (Khandelwal et al., 2010; Su et al., 2008).”
BackgroundWalker, D. G., Lue, L.-F., Tang, T. M., Adler, C. H., Caviness, J. N., Sabbagh, M. N., Serrano, G. E., Sue, L. I., & Beach, T. G. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.03.007 · Cited by 33
“To obtain adequate sample sizes of each stage, cases were from several different LB disease classifications, including incidental Lewy body disease (ILBD), Alzheimer’s disease with Lewy bodies (ADLB), PD, PD with dementia (PDD) and DLB.”
BackgroundInfluentialCurrent Development of Acupuncture Research in Parkinson's Disease
Zeng, B., Salvage, S., & Jenner, P. G. (2013) · International review of neurobiology · doi:10.1016/b978-0-12-411545-3.00007-9 · Cited by 32
Boi, L., Pisanu, A., Palmas, M. F., Fusco, G., Carboni, E., Casu, M. A., Satta, V., Scherma, M., Janda, E., Mocci, I., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228535 · Cited by 33
Recent advances in dopamine D 2 receptor ligands in the treatment of neuropsychiatric disorders
Jůza, R., Musílek, K., Mezeiová, E., Soukup, O., & Korábečný, J. (2022) · Medicinal Research Reviews · doi:10.1002/med.21923 · Cited by 34
Tweedie, D., Frankola, K. A., Luo, W., Li, Y., & Greig, N. H. (2011) · The Open Biochemistry Journal · doi:10.2174/1874091x01105010037 · Cited by 32
Evidence for immune system alterations in peripheral biological fluids in Parkinson’s disease
Bartl, M., Xylaki, M., Bähr, M., Weber, S., Trenkwalder, C., & Mollenhauer, B. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105744 · Cited by 33
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Harnessing the Therapeutic Potential of the Nrf2/Bach1 Signaling Pathway in Parkinson’s Disease
Ahuja, M., Kaidery, N. A., Dutta, D., Attucks, O. C., Kazakov, E. H., Gazaryan, I. G., Matsumoto, M., Igarashi, K., Sharma, S. M., & Thomas, B. (2022) · Antioxidants · doi:10.3390/antiox11091780 · Cited by 34
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“Our studies have observed that chronic MC-LR exposure causes abnormal expression of α-syn in neurons, and α-syn has been proven to be an important trigger for the activation of microglia [26, 27].”
BackgroundA Combined Panel of Salivary Biomarkers in de novo Parkinson's Disease
Bartolo, M. I. D., Vivacqua, G., Belvisi, D., Mancinelli, R., Fabbrini, A., Manzo, N., Costanzo, M., Leodori, G., Conte, A., Fabbrini, G., et al. (2022) · Annals of Neurology · doi:10.1002/ana.26550 · Cited by 32
“TNFalpha is specifically produced by macrophages and microglia and has been detected in the brain of animal models of synucleinopathies presenting with microglial activation.(40,41) Histological analyses have also shown that the peripheral nervous system and the gastrointestinal tract are affected by both a-syn aggreg…”
BackgroundApoptosis signal-regulating kinase 1 modulates the phenotype of α-synuclein transgenic mice
Lee, K. W., Woo, J.-M., Im, J. Y., Park, E. S., He, L., Ichijo, H., Junn, E., & Mouradian, M. M. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.07.034 · Cited by 32
“Mounting evidence suggests that accumulation of a-synuclein and its protofibrils stimulates microglial activation and cytokine production (Alvarez-Erviti et al., 2011; Klegeris, et al., 2008; Lee et al., 2010; Su et al., 2008; Zhang et al., 2005).”
InfluentialParkinson’s Disease: Can Targeting Inflammation Be an Effective Neuroprotective Strategy?
Gundersen, V. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.580311 · Cited by 33
CD36: A multi‐modal target for acute stroke therapy
Cho, S., & Kim, E. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05801.x · Cited by 31
“The pro-inflammatory nature of CD36 has been implicated in atherosclerosis (Febbraio et al. 2000), Alzheimer’s disease (El Khoury et al. 2003), and Parkinson’s disease (Su et al. 2007).”
BackgroundMore, S. V., Kumar, H., Kim, I., Koppula, S., Kim, B.-W., & Choi, D. (2013) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/18715273113129990059 · Cited by 31
The Role of Glial Mitochondria in α-Synuclein Toxicity
Jeon, Y., Kwon, Y., Jo, M., Lee, S., Kim, S., & Kim, H. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.548283 · Cited by 31
Duwa, R., Jeong, J., & Yook, S. (2021) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-021-00521-3 · Cited by 31
GCH1 Deficiency Activates Brain Innate Immune Response and Impairs Tyrosine Hydroxylase Homeostasis
Larbalestier, H., Keatinge, M., Watson, L., White, E., Gowda, S. B., Wei, W., Koler, K., Semenova, S. A., Elkin, A. M., Rimmer, N., et al. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0653-21.2021 · Cited by 30
Molecular and Neurochemical Mechanisms in PD Pathogenesis
Paris, I. B., Lozano, J., Perez-Pastene, C., Muñoz, P., & Segura‐Aguilar, J. (2009) · Neurotoxicity Research · doi:10.1007/s12640-009-9059-4 · Cited by 29
“Early microglial activation with concomitant increase in proinflammatory molecules in mice that over-express wildtype SYN was observed (Su et al. 2008).”
From Synaptic Protein to Prion: The Long and Controversial Journey of α-Synuclein
Heras‐Garvin, A., & Stefanova, N. (2020) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2020.584536 · Cited by 31
Zhang, Y., Zhang, D., Gao, Y., Li, Y., Tao, Y., Xu, H., Man, S., Zhang, M., & Xu, Y. (2021) · Current Eye Research · doi:10.1080/02713683.2021.1933054 · Cited by 28
Gut microbiota, pathogenic proteins and neurodegenerative diseases
Wei, W., Wang, S., Xu, C., Zhou, X., Lian, X., He, L., & Li, K. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.959856 · Cited by 30
“, 2015), and promotes the production of ROS, TNF-α, IL-1β, COX2, iNOS and other inflammatory factors in microglia (Su et al., 2008; Watson et al., 2012).”
BackgroundMixed pathology as a rule, not exception: Time to reconsider disease nosology
Chu, Y., Hirst, W. D., & Kordower, J. H. (2023) · Handbook of clinical neurology · doi:10.1016/b978-0-323-85538-9.00012-2 · Cited by 28
Shakola, F., Suri, P., & Ruggiu, M. (2015) · Biomolecules · doi:10.3390/biom5032073 · Cited by 28
“Misfolded alpha-synuclein protein (SNCA) activates microglia in vitro, leading to the secretion of pro-inflammatory cytokines, such as TNF- [53] and IL-1 [54], and to the production of reactive oxygen species, ultimately damaging DA neurons [55].”
BackgroundNon-cell-autonomous actions of α-synuclein: Implications in glial synucleinopathies
Lim, S., Kim, H., Kim, D., & Lee, S. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.06.010 · Cited by 28
CRISPR/Cas9 Editing for Gaucher Disease Modelling
Pavan, E., Ormazábal, M., Peruzzo, P., Vaena, E., Rozenfeld, P. A., & Dardis, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093268 · Cited by 27
Beal, M. F., Chiluwal, J., Calingasan, N. Y., Milne, G. L., Shchepinov, M. S., & Tapias, V. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01090-6 · Cited by 29
Ho, D. H., Nam, D., Seo, M. K., Park, S., Seol, W., & Son, I. (2022) · Cells · doi:10.3390/cells11050861 · Cited by 27
Iba, M., McDevitt, R. A., Kim, C., Roy, R., Sarantopoulou, D., Tommer, E., Siegars, B., Sallin, M. A., Kwon, S., Sen, J. M., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00564-6 · Cited by 26
“As we and others have shown that innate cells play a role in the pathogenesis of DLB/PD in ɑ -syn transgenic models [50, 51], we investigated the contribution of aging on microglial and astroglial cells in the ɑ -syn pff model.”
BackgroundRetractedBennett, N. K., Chmielowski, R., Abdelhamid, D. S., Faig, J. J., Francis, N. L., Baum, J., Pang, Z. P., Uhrich, K. E., & Moghe, P. V. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.10.001 · Cited by 27
Targets and Mechanisms in Prevention of Parkinson's Disease through Immunomodulatory Treatments
Chelpin, M. V. E., & Vorup‐Jensen, T. (2017) · Scandinavian Journal of Immunology · doi:10.1111/sji.12542 · Cited by 27
In Search of Effective Treatments Targeting α-Synuclein Toxicity in Synucleinopathies: Pros and Cons
Fouka, M., Mavroeidi, P., Tsaka, G., & Xilouri, M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.559791 · Cited by 27
Mutations in GBA and LRRK2 Are Not Associated with Increased Inflammatory Markers
Thaler, A., Omer, N., Giladi, N., Gurevich, T., Bar‐Shira, A., Gana‐Weisz, M., Goldstein, O., Kestenbaum, M., Shirvan, J. C., Cedarbaum, J. M., et al. (2021) · Journal of Parkinson s Disease · doi:10.3233/jpd-212624 · Cited by 27
GCH1 deficiency activates brain innate immune response and impairs tyrosine hydroxylase homeostasis
Larbalestier, H., Keatinge, M., Watson, L., White, E., Gowda, S., Wei, W., Koler, K., Semenova, S., Elkin, A., Rimmer, N., et al. (2022) · White Rose Research Online (University of Leeds, The University of Sheffield, University of York) · Cited by 26
Lü, L., Liu, X., Fu, J., Liang, J., Hou, Y., & Dou, H. (2022) · Scientific Reports · doi:10.1038/s41598-022-10973-8 · Cited by 26
Rauschenberger, L., Behnke, J. K., Grotemeyer, A., Knörr, S., Volkmann, J., & Ip, C. W. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105798 · Cited by 29
“In a mouse model overexpressing human wildtype (wt) α-synuclein driven by a TH promoter, microglia activation was significantly increased in the SN of young transgenic (tg) mice compared to C57BL/6 control mice (Su et al., 2008).”
Reduction of αSYN Pathology in a Mouse Model of PD Using a Brain-Penetrating Bispecific Antibody
Roshanbin, S., Julku, U. H., Xiong, M., Eriksson, J., Masliah, E., Hultqvist, G., Bergström, J. J. E., Ingelsson, M., Syvänen, S., & Sehlin, D. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14071412 · Cited by 30
Hapln2 in Neurological Diseases and Its Potential as Therapeutic Target
Wang, Q., Wang, C., Ji, B., Zhou, J., Yang, C., & Chen, J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00060 · Cited by 27
Investigating the Convergent Mechanisms between Major Depressive Disorder and Parkinson’s Disease
Tran, A. A., Smet, M. D., Grant, G. D., Khoo, T. K., & Pountney, D. L. (2020) · Complex Psychiatry · doi:10.1159/000512657 · Cited by 29
Abdi, I. Y., Bartl, M., Dakna, M., Abdesselem, H., Majbour, N. K., Trenkwalder, C., El‐Agnaf, O. M. A., & Mollenhauer, B. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.105997 · Cited by 26
Hippocampal proliferation is increased in presymptomatic Parkinson’s disease and due to microglia
Doorn, K. J., Drukarch, B., van Dam, A.-M., & Lucassen, P. J. (2014) · Neural Plasticity · doi:10.1155/2014/959154 · Cited by 24
“While in vitro studies had already demonstrated that the aggregated form of α-synuclein can trigger microglial activation [10, 68], the HC of iLBD cases is largely devoid of α-synuclein depositions, and a role for soluble forms or αsynuclein oligomers can thus not be excluded.”
Tarale, P., & Alam, M. M. (2022) · Inflammopharmacology · doi:10.1007/s10787-022-00958-4 · Cited by 26
TNFα increases tyrosine hydroxylase expression in human monocytes
Gopinath, A., Badov, M., Francis, M. L., Shaw, G., Collins, A., Miller, D. R., Hansen, C. A., Mackie, P. M., Tansey, M. G., Dagra, A., et al. (2021) · npj Parkinson s Disease · doi:10.1038/s41531-021-00201-x · Cited by 23
Cheon, S. Y., Kim, J., Kim, S. Y., Kim, E. J., & Koo, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031103 · Cited by 24
Hull, A. J., Atilano, M. L., Gergi, L., & Kinghorn, K. J. (2024) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2022.0381 · Cited by 24
“Several studies have suggested that α Syn is a damage-associated molecular pattern (DAMP) that can induce production of inflammatory cytokines in microglia [99 – 101].”
Genome-wide transcriptome architecture in a mouse model of Gulf War Illness
Xu, F., Ashbrook, D. G., Gao, J. L., Starlard‐Davenport, A., Zhao, W., Miller, D. B., O'Callaghan, J. P., Williams, R. W., Jones, B. C., & Lu, L. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.06.018 · Cited by 22
“, 2003), and peripheral nervous system regeneration (Su et al., 2008), and have been implicated in a wide variety of brain diseases, ranging from stroke to neurodegeneration (Garcia-Bonilla et al.”
BackgroundBilirubin: A Promising Therapy for Parkinson’s Disease
Jayanti, S. D., Moretti, R., Tiribelli, C., & Gazzin, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126223 · Cited by 23
“For instance, in primary cultures, α-synuclein mediates dose-dependent activation of microglia [50].”
BackgroundPattarini, R., Rong, Y., Qu, C., & Morgan, J. I. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.06.064 · Cited by 22
“Several functions have been ascribed to this protein such as: activation of microglia (Su et al., 2007), modulation of glutamatergic (Gureviciene et al.”
Background
Metadata
- Authors
- Su, X., Maguire-Zeiss, K. A., Giuliano, R., Prifti, L., Venkatesh, K., & Federoff, H. J.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Federoff, Howard J.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 29
- Issue
- 11
- Pages
- 1690-1701
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC2621109
- OpenAlex
- W2120997873
- Cited by
- 474
- References
- 86
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 27 · 2023: 19 · 2022: 46 · 2021: 46 · 2020: 37 · 2019: 30 · 2018: 26 · 2017: 18 · 2016: 15 · 2015: 22 · 2014: 32 · 2013: 21 · 2012: 24
- FWCI
- 12.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (T32NS007489)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, alpha-synuclein, microglial activation, neuroinflammation, CD36 scavenger receptor, proinflammatory molecules, Lewy bodies, MN9D cells, pathogenesis
- MeSH terms
- Animals, Cell Line, Disease Models, Animal, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Cytokines, Microglia, Parkinsonian Disorders, Mice, Synucleins
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