Differential LRRK2 Signalling and Gene Expression in WT-LRRK2 and G2019S-LRRK2 Mouse Microglia Treated with Zymosan and MLi2
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals and Primary Microglia Cultures and Treatment
2.2. Protein Assay
2.3. Zymosan and MLi-2 Treatment Protocol
2.4. Immunoblots and Fluorescent Blots
2.5. RNA Sequencing (RNA-Seq)
2.6. Analysing RNA-Seq Data
2.7. Statistical Analyses
3. Results
3.1. Zymosan Induces Phosphorylation of LRRK2 in Microglia
3.2. Differential Gene Expression between Wild-Type and G2019S-LRRK2 with Zymosan and MLi-2
3.3. Functional Enrichment Analysis in Wild-Type and G2019S-LRRK2 with Zymosan and MLi-2
3.4. Basal Level of Significant Differentially Expressed Genes in the Wild-Type and G2019S-LRRK2 Genotype
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Johnson, M.E.; Stecher, B.; Labrie, V.; Brundin, L.; Brundin, P. Triggers, Facilitators, and Aggravators: Redefining Parkinson’s Disease Pathogenesis. Trends Neurosci. 2019, 42, 4–13. [Google Scholar] [CrossRef] [PubMed]
- Cherian, A.; Divya, K.P. Genetics of Parkinson’s disease. Acta Neurol. Belg. 2020, 120, 1297–1305. [Google Scholar] [CrossRef] [PubMed]
- McGeer, P.L.; Itagaki, S.; Boyes, B.E.; McGeer, E.G. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 1988, 38, 1285–1291. [Google Scholar] [CrossRef] [PubMed]
- Mogi, M.; Harada, M.; Kondo, T.; Riederer, P.; Inagaki, H.; Minami, M.; Nagatsu, T. Interleukin-1β, interleukin-6, epidermal growth factor and transforming growth factor-α are elevated in the brain from parkinsonian patients. Neurosci. Lett. 1994, 180, 147–150. [Google Scholar] [CrossRef] [PubMed]
- Mogi, M.; Harada, M.; Riederer, P.; Narabayashi, H.; Fujita, K.; Nagatsu, T. Tumor necrosis factor-α (TNF-α) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci. Lett. 1994, 165, 208–210. [Google Scholar] [CrossRef]
- Fiszer, U.; Mix, E.; Fredrikson, S.; Kostulas, V.; Olsson, T.; Link, H. γδ+ T cells are increased in patients with Parkinson’s disease. J. Neurol. Sci. 1994, 121, 39–45. [Google Scholar] [CrossRef]
- Blum-Degena, D.; Müller, T.; Kuhn, W.; Gerlach, M.; Przuntek, H.; Riederer, P. Interleukin-1β and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci. Lett. 1995, 202, 17–20. [Google Scholar] [CrossRef]
- Ren, C.; Ding, Y.; Wei, S.; Guan, L.; Zhang, C.; Ji, Y.; Wang, F.; Yin, S.; Yin, P. G2019S Variation in LRRK2: An Ideal Model for the Study of Parkinson’s Disease? Front. Hum. Neurosci. 2019, 13, 306. [Google Scholar] [CrossRef]
- Thévenet, J.; Gobert, R.P.; van Huijsduijnen, R.H.; Wiessner, C.; Sagot, Y.J. Regulation of LRRK2 expression points to a functional role in human monocyte maturation. PLoS ONE 2011, 6, e21519. [Google Scholar] [CrossRef]
- Moehle, M.S.; Webber, P.J.; Tse, T.; Sukar, N.; Standaert, D.G.; DeSilva, T.M.; Cowell, R.M.; West, A.B. LRRK2 inhibition attenuates microglial inflammatory responses. J. Neurosci. 2012, 32, 1602–1611. [Google Scholar] [CrossRef]
- Daher, J.P.L.; Volpicelli-Daley, L.A.; Blackburn, J.P.; Moehle, M.S.; West, A.B. Abrogation of α-synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats. Proc. Natl. Acad. Sci. USA 2014, 111, 9289–9294. [Google Scholar] [CrossRef] [PubMed]
- Langston, R.G.; Beilina, A.; Reed, X.; Kaganovich, A.; Singleton, A.B.; Blauwendraat, C.; Gibbs, J.R.; Cookson, M.R. Association of a common genetic variant with Parkinson’s disease is mediated by microglia. Sci. Transl. Med. 2022, 14, eabp8869. [Google Scholar] [CrossRef] [PubMed]
- Russo, I.; Bubacco, L.; Greggio, E. LRRK2 as a target for modulating immune system responses. Neurobiol. Dis. 2022, 169, 105724. [Google Scholar] [CrossRef] [PubMed]
- Nazish, I.; Arber, C.; Piers, T.M.; Warner, T.T.; Hardy, J.A.; Lewis, P.A.; Pocock, J.M.; Bandopadhyay, R. Abrogation of LRRK2 dependent Rab10 phosphorylation with TLR4 activation and alterations in evoked cytokine release in immune cells. Neurochem. Int. 2021, 147, 105070. [Google Scholar] [CrossRef] [PubMed]
- Nichols, R.J.; Dzamko, N.; Morrice, N.A.; Campbell, D.G.; Deak, M.; Ordureau, A.; Macartney, T.; Tong, Y.; Shen, J.; Prescott, A.R.; et al. 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson’s disease-associated mutations and regulates cytoplasmic localization. Biochem. J. 2010, 430, 393–404. [Google Scholar] [CrossRef] [PubMed]
- Dzamko, N.; Inesta-Vaquera, F.; Zhang, J.; Xie, C.; Cai, H.; Arthur, S.; Tan, L.; Choi, H.; Gray, N.; Cohen, P.; et al. The IkappaB kinase family phosphorylates the Parkinson’s disease kinase LRRK2 at Ser935 and Ser910 during Toll-like receptor signaling. PLoS ONE 2012, 7, e39132. [Google Scholar] [CrossRef] [PubMed]
- Schapansky, J.; Nardozzi, J.D.; Felizia, F.; LaVoie, M.J. Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy. Hum. Mol. Genet. 2014, 23, 4201–4214. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.; Flynn, R.; Sharma, I.; Haberman, E.; Carling, P.J.; Nicholls, F.J.; Stegmann, M.; Vowles, J.; Haenseler, W.; Wade-Martins, R.; et al. LRRK2 Is Recruited to Phagosomes and Co-recruits RAB8 and RAB10 in Human Pluripotent Stem Cell-Derived Macrophages. Stem Cell Rep. 2020, 14, 940–955. [Google Scholar] [CrossRef]
- Russo, I.; Berti, G.; Plotegher, N.; Bernardo, G.; Filograna, R.; Bubacco, L.; Greggio, E. Leucine-rich repeat kinase 2 positively regulates inflammation and down-regulates NF-κB p50 signaling in cultured microglia cells. J. Neuroinflammation 2015, 12, 230. [Google Scholar] [CrossRef]
- Elcombe, S.E.; Naqvi, S.; Bosch, M.W.M.V.D.; MacKenzie, K.F.; Cianfanelli, F.; Brown, G.D.; Arthur, J.S.C. Dectin-1 regulates IL-10 production via a MSK1/2 and CREB dependent pathway and promotes the induction of regulatory macrophage markers. PLoS ONE 2013, 8, e60086. [Google Scholar] [CrossRef]
- Kluss, J.H.; Conti, M.M.; Kaganovich, A.; Beilina, A.; Melrose, H.L.; Cookson, M.R.; Mamais, A. Detection of endogenous S1292 LRRK2 autophosphorylation in mouse tissue as a readout for kinase activity. NPJ Park. Dis. 2018, 4, 13. [Google Scholar] [CrossRef] [PubMed]
- Tasegian, A.; Singh, F.; Ganley, I.G.; Reith, A.D.; Alessi, D.R. Impact of Type II LRRK2 inhibitors on signaling and mitophagy. Biochem. J. 2021, 478, 3555–3573. [Google Scholar] [CrossRef] [PubMed]
- Dobin, A.; Davis, C.A.; Schlesinger, F.; Drenkow, J.; Zaleski, C.; Jha, S.; Batut, P.; Chaisson, M.; Gingeras, T.R. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 2013, 29, 15–21. [Google Scholar] [CrossRef] [PubMed]
- Roberts, A.; Pachter, L. Streaming fragment assignment for real-time analysis of sequencing experiments. Nat. Methods 2013, 10, 71–73. [Google Scholar] [CrossRef]
- Love, M.I.; Huber, W.; Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014, 15, 550. [Google Scholar] [CrossRef]
- Marchand, A.; Drouyer, M.; Sarchione, A.; Chartier-Harlin, M.-C.; Taymans, J.-M. LRRK2 Phosphorylation, More Than an Epiphenomenon. Front. Neurosci. 2020, 14, 527. [Google Scholar] [CrossRef]
- Chia, R.; Haddock, S.; Beilina, A.; Rudenko, I.N.; Mamais, A.; Kaganovich, A.; Li, Y.; Kumaran, R.; Nalls, M.A.; Cookson, M.R. Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7. Nat. Commun. 2014, 5, 5827. [Google Scholar] [CrossRef]
- Mamais, A.; Kluss, J.H.; Bonet-Ponce, L.; Landeck, N.; Langston, R.G.; Smith, N.; Beilina, A.; Kaganovich, A.; Ghosh, M.C.; Pellegrini, L.; et al. Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia. PLOS Biol. 2021, 19, e3001480. [Google Scholar] [CrossRef]
- Nalls, M.A.; Blauwendraat, C.; Vallerga, C.L.; Heilbron, K.; Bandres-Ciga, S.; Chang, D.; Tan, M.; Kia, D.A.; Noyce, A.J.; Xue, A.; et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: A meta-analysis of genome-wide association studies. Lancet Neurol. 2019, 18, 1091–1102. [Google Scholar] [CrossRef]
- Wilms, H.; Rosenstiel, P.; Sievers, J.; Deuschl, G.; Zecca, L.; Lucius, R.; Zhang, W.; Wang, T.; Pei, Z.; Miller, D.S.; et al. Activation of microglia by human neuromelanin is NF-κB-dependent and involves p38 mitogen-activated protein kinase: Implications for Parkinson’s disease. FASEB J. 2003, 17, 500–502. [Google Scholar] [CrossRef]
- He, Y.; Le, W.-D.; Appel, S.H. Role of Fcγ Receptors in nigral cell injury induced by Parkinson disease immunoglobulin injection into mouse substantia nigra. Exp. Neurol. 2002, 176, 322–327. [Google Scholar] [CrossRef] [PubMed]
- Perry, V.H.; Holmes, C. Microglial priming in neurodegenerative disease. Nat. Rev. Neurol. 2014, 10, 217–224. [Google Scholar] [CrossRef] [PubMed]
- Garden, G.A.; Möller, T. Microglia biology in health and disease. J. Neuroimmune Pharmacol. 2006, 1, 127–137. [Google Scholar] [CrossRef] [PubMed]
- Russo, I.; Kaganovich, A.; Ding, J.; Landeck, N.; Mamais, A.; Varanita, T.; Biosa, A.; Tessari, I.; Bubacco, L.; Greggio, E.; et al. Transcriptome analysis of LRRK2 knock-out microglia cells reveals alterations of inflammatory- and oxidative stress-related pathways upon treatment with α-synuclein fibrils. Neurobiol. Dis. 2019, 129, 67–78. [Google Scholar] [CrossRef] [PubMed]
- Pulido-Salgado, M.; Vidal-Taboada, J.M.; Barriga, G.G.-D.; Solà, C.; Saura, J. RNA-Seq transcriptomic profiling of primary murine microglia treated with LPS or LPS + IFNγ. Sci. Rep. 2018, 8, 16096. [Google Scholar] [CrossRef] [PubMed]
- Egami, Y.; Fujii, M.; Kawai, K.; Ishikawa, Y.; Fukuda, M.; Araki, N. Activation-Inactivation Cycling of Rab35 and ARF6 Is Required for Phagocytosis of Zymosan in RAW264 Macrophages. J. Immunol. Res. 2015, 2015, 429439. [Google Scholar] [CrossRef]
- Ozinsky, A.; Underhill, D.M.; Fontenot, J.D.; Hajjar, A.M.; Smith, K.D.; Wilson, C.B.; Schroeder, L.; Aderem, A. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors. Proc. Natl. Acad. Sci. USA 2000, 97, 13766–13771. [Google Scholar] [CrossRef]
- Le Cabec, V.; Carréno, S.; Moisand, A.; Bordier, C.; Maridonneau-Parini, I. Complement receptor 3 (CD11b/CD18) mediates type I and type II phagocytosis during nonopsonic and opsonic phagocytosis, respectively. J. Immunol. 2002, 169, 2003–2009. [Google Scholar] [CrossRef]
- Herre, J.; Marshall, A.S.; Caron, E.; Edwards, A.D.; Williams, D.L.; Schweighoffer, E.; Brown, G.D. Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages. Blood 2004, 104, 4038–4045. [Google Scholar] [CrossRef]
- Wall, E.A.; Zavzavadjian, J.R.; Chang, M.S.; Randhawa, B.; Zhu, X.; Hsueh, R.C.; Liu, J.; Driver, A.; Bao, X.R.; Sternweis, P.C.; et al. Suppression of LPS-Induced TNF-α Production in Macrophages by cAMP Is Mediated by PKA-AKAP95-p105. Sci. Signal. 2009, 2, ra28. [Google Scholar] [CrossRef]
- Jiang, L.I.; Sternweis, P.C.; Wang, J.E. Zymosan activates protein kinase A via adenylyl cyclase VII to modulate innate immune responses during inflammation. Mol. Immunol. 2012, 54, 14–22. [Google Scholar] [CrossRef] [PubMed]
- Gardet, A.; Benita, Y.; Li, C.; Sands, B.E.; Ballester, I.; Stevens, C.; Korzenik, J.R.; Rioux, J.D.; Daly, M.J.; Xavier, R.J.; et al. LRRK2 is involved in the IFN-γ response and host response to pathogens. J. Immunol. 2010, 185, 5577–5585. [Google Scholar] [CrossRef] [PubMed]
- Liu, W.; Liu, X.; Li, Y.; Zhao, J.; Liu, Z.; Hu, Z.; Wang, Y.; Yao, Y.; Miller, A.W.; Su, B.; et al. LRRK2 promotes the activation of NLRC4 inflammasome during Salmonella Typhimurium infection. J. Exp. Med. 2017, 214, 3051–3066. [Google Scholar] [CrossRef] [PubMed]
- Shutinoski, B.; Hakimi, M.; Harmsen, I.E.; Lunn, M.; Rocha, J.; Lengacher, N.; Zhou, Y.Y.; Khan, J.; Nguyen, A.; Hake-Volling, Q.; et al. Lrrk2 alleles modulate inflammation during microbial infection of mice in a sex-dependent manner. Sci. Transl. Med. 2019, 11. [Google Scholar] [CrossRef] [PubMed]
- Wang, D.-M.; Li, F.-J.; Zheng, S.-R. Adrenomedullin: An important participant in neurological diseases. Neural Regen. Res. 2020, 15, 1199–1207. [Google Scholar] [CrossRef]
- West, A.R.; Tseng, K.Y. Nitric Oxide–Soluble Guanylyl Cyclase–Cyclic GMP Signaling in the Striatum: New Targets for the Treatment of Parkinson’s Disease? Front. Syst. Neurosci. 2011, 5, 55. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Wu, X.; Liu, S.; Zhao, Y.; Zhu, J.; Liu, K. Roles of Neuropeptide Y in Neurodegenerative and Neuroimmune Diseases. Front. Neurosci. 2019, 13, 869. [Google Scholar] [CrossRef]
- Dzamko, N.; Zhou, J.; Huang, Y.; Halliday, G.M. Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis. Front. Mol. Neurosci. 2014, 7, 57. [Google Scholar] [CrossRef]
- Perner, C.; Perner, F.; Gaur, N.; Zimmermann, S.; Witte, O.W.; Heidel, F.H.; Grosskreutz, J.; Prell, T. Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease. J. Neuroinflammation 2019, 16, 94. [Google Scholar] [CrossRef]
- Garcia-Reitboeck, P.; Phillips, A.; Piers, T.M.; Villegas-Llerena, C.; Butler, M.; Mallach, A.; Pocock, J.M. Human induced pluripotent stem cell derived microglia-like cellsharbouring TREM2 missense mutations show specific deficits in phagocytosis. Cell Rep. 2018, 24, 2300. [Google Scholar] [CrossRef]
- van den Pol, A.N. Viral infections in the developing and mature brain. Trends Neurosci. 2006, 29, 398–406. [Google Scholar] [CrossRef] [PubMed]
- Wang, T.; Town, T.; Alexopoulou, L.; Anderson, J.F.; Fikrig, E.; Flavell, R.A. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat. Med. 2004, 10, 1366–1373. [Google Scholar] [CrossRef] [PubMed]
- Herbst, S.; Campbell, P.; Harvey, J.; Bernard, E.M.; Papayannopoulos, V.; Wood, N.W.; Morris, H.R.; Gutierrez, M.G. LRRK 2 activation controls the repair of damaged endomembranes in macrophages. EMBO J. 2020, 39, e104494. [Google Scholar] [CrossRef] [PubMed]
- Weindel, C.G.; Bell, S.L.; Vail, K.J.; O West, K.; Patrick, K.L.; O Watson, R. LRRK2 maintains mitochondrial homeostasis and regulates innate immune responses to Mycobacterium tuberculosis. eLife 2020, 9, e51071. [Google Scholar] [CrossRef] [PubMed]
- Murthy, M.N.; Ukbec; Blauwendraat, C.; Guelfi, S.; Hardy, J.; Lewis, P.A.; Trabzuni, D. Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson’s disease on chromosome 7p15.3. Neurogenetics 2017, 18, 121–133. [Google Scholar] [CrossRef] [PubMed]
- Diaz-Ortiz, M.E.; Seo, Y.; Posavi, M.; Cordon, M.C.; Clark, E.; Jain, N.; Charan, R.; Gallagher, M.D.; Unger, T.L.; Amari, N.; et al. GPNMB confers risk for Parkinson’s disease through interaction with α-synuclein. Science 2022, 377, eabk0637. [Google Scholar] [CrossRef]
- Satoh, J.-I.; Kino, Y.; Yanaizu, M.; Ishida, T.; Saito, Y. Microglia express GPNMB in the brains of Alzheimer’s disease and Nasu-Hakola disease. Intractable Rare Dis. Res. 2019, 8, 120–128. [Google Scholar] [CrossRef] [PubMed]
- Milanowski, L.M.; Hou, X.; Bredenberg, J.M.; Fiesel, F.C.; Cocker, L.T.; Soto-Beasley, A.I.; Walton, R.L.; Strongosky, A.J.; Faroqi, A.H.; Barcikowska, M.; et al. Cathepsin B p.Gly284Val Variant in Parkinson’s Disease Pathogenesis. Int. J. Mol. Sci. 2022, 23, 7086. [Google Scholar] [CrossRef]
- Blauwendraat, C.; Reed, X.; Krohn, L.; Heilbron, K.; Bandres-Ciga, S.; Tan, M.; Gibbs, J.R.; Hernandez, D.G.; Kumaran, R.; Langston, R.; et al. Genetic modifiers of risk and age at onset in GBA associated Parkinson’s disease and Lewy body dementia. Brain 2020, 143, 234–248. [Google Scholar] [CrossRef]
- Man, S.M.; Kanneganti, T.-D. Regulation of lysosomal dynamics and autophagy by CTSB/cathepsin B. Autophagy 2016, 12, 2504–2505. [Google Scholar] [CrossRef]
- Vasiljeva, O.; Reinheckel, T.; Peters, C.; Turk, D.; Turk, V.; Turk, B. Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr. Pharm. Des. 2007, 13, 387–403. [Google Scholar] [CrossRef] [PubMed]
- McGlinchey, R.P.; Lee, J.C. Cysteine cathepsins are essential in lysosomal degradation of α-synuclein. Proc. Natl. Acad. Sci. USA 2015, 112, 9322–9327. [Google Scholar] [CrossRef] [PubMed]
- Steinfeld, R.; Reinhardt, K.; Schreiber, K.; Hillebrand, M.; Kraetzner, R.; Brück, W.; Saftig, P.; Gärtner, J. Cathepsin D deficiency is associated with a human neurodegenerative disorder. Am. J. Hum. Genet. 2006, 78, 988–998. [Google Scholar] [CrossRef] [PubMed]
- Siintola, E.; Partanen, S.; Strömme, P.; Haapanen, A.; Haltia, M.; Maehlen, J.; Lehesjoki, A.-E.; Tyynelä, J. Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis. Brain 2006, 129, 1438–1445. [Google Scholar] [CrossRef]
- Yadavalli, N.; Ferguson, S.M. LRRK2 negatively regulates the abundance of multiple lysosomal proteins and the G2019S LRRK2 mutation suppresses lysosomal proteolytic activity in macrophages. Proc. Natl. Acad. Sci. USA 2023, 120, e2303789120. [Google Scholar] [CrossRef]
- Alexander, G.E. Biology of Parkinson’s disease: Pathogenesis and pathophysiology of a multisystem neurodegenerative disorder. Dialogues Clin. Neurosci. 2004, 6, 259–280. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Nazish, I.; Mamais, A.; Mallach, A.; Bettencourt, C.; Kaganovich, A.; Warner, T.; Hardy, J.; Lewis, P.A.; Pocock, J.; Cookson, M.R.; et al. Differential LRRK2 Signalling and Gene Expression in WT-LRRK2 and G2019S-LRRK2 Mouse Microglia Treated with Zymosan and MLi2. Cells 2024, 13, 53. https://doi.org/10.3390/cells13010053
Nazish I, Mamais A, Mallach A, Bettencourt C, Kaganovich A, Warner T, Hardy J, Lewis PA, Pocock J, Cookson MR, et al. Differential LRRK2 Signalling and Gene Expression in WT-LRRK2 and G2019S-LRRK2 Mouse Microglia Treated with Zymosan and MLi2. Cells. 2024; 13(1):53. https://doi.org/10.3390/cells13010053
Chicago/Turabian StyleNazish, Iqra, Adamantios Mamais, Anna Mallach, Conceicao Bettencourt, Alice Kaganovich, Thomas Warner, John Hardy, Patrick A. Lewis, Jennifer Pocock, Mark R. Cookson, and et al. 2024. "Differential LRRK2 Signalling and Gene Expression in WT-LRRK2 and G2019S-LRRK2 Mouse Microglia Treated with Zymosan and MLi2" Cells 13, no. 1: 53. https://doi.org/10.3390/cells13010053
APA StyleNazish, I., Mamais, A., Mallach, A., Bettencourt, C., Kaganovich, A., Warner, T., Hardy, J., Lewis, P. A., Pocock, J., Cookson, M. R., & Bandopadhyay, R. (2024). Differential LRRK2 Signalling and Gene Expression in WT-LRRK2 and G2019S-LRRK2 Mouse Microglia Treated with Zymosan and MLi2. Cells, 13(1), 53. https://doi.org/10.3390/cells13010053