{"id":4020,"date":"2023-12-05T13:13:26","date_gmt":"2023-12-05T11:13:26","guid":{"rendered":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/?page_id=4020"},"modified":"2025-10-06T11:28:09","modified_gmt":"2025-10-06T08:28:09","slug":"microglia-in-%ce%b1-synucleinopathies","status":"publish","type":"page","link":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/microglia-in-%ce%b1-synucleinopathies\/","title":{"rendered":"Microglia in \u03b1-synucleinopathies"},"content":{"rendered":"\n<p>Microglia phagocytose \u03b1-synuclein aggregates which leads to release of proinflammatory cytokines, and in contrast, we have shown that presence of these cytokines may inhibit phagocytosis of aberrant proteins by human microglia (Niskanen et al., 2024). This causes inflammatory damage to neighbouring cells, leading to fewer microglia being able to take up and degrade \u03b1-synuclein, resulting in a cycle of neuroinflammation and protein aggregation that may cause further dysfunction and damage to surrounding cells.<\/p>\n\n\n\n<p>Human microglia have differential gene expression compared to mouse, including higher expression of Parkinson\u2019s-related genes, therefore studies carried out in rodent models alone do not translate to humans due to differences in microglial biology. Further, these highly reactive cells behave differently <em>in vitro<\/em> compared to <em>in vivo<\/em>, meaning that <em>in vitro<\/em> findings may not always translate to the <em>in vivo<\/em> situation. To address this, we established a novel model: transplantation of human microglia progenitors from induced pluripotent stem cells to an immunodeficient mouse model of Parkinson\u2019s disease (Albert et al., 2025). We observed a human-specific effect of microglia on the \u03b1-synuclein aggregates, resulting in neuroprotection in the model. We now aim to elucidate this further.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"622\" src=\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2025\/02\/image-1024x622.png\" alt=\"\" class=\"wp-image-4171\" srcset=\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2025\/02\/image-1024x622.png 1024w, https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2025\/02\/image-300x182.png 300w, https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2025\/02\/image-768x467.png 768w, https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2025\/02\/image.png 1047w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<p>Top: Immunohistochemical staining of the mouse substantia nigra area with alpha-synuclein phosphorylated at serine-129 in the tyrosine hydroxylase cell bodies and surroundings. Bottom: Human microglia progenitors derived from induced pluripotent stem cells were transplanted to the mouse brain and 3 months later show a mature, brain-resident phenotype at the protein level.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Publications<\/h2>\n\n\n\n<p><strong>Albert, K.<\/strong>, Peltonen, S., Vanne, A., K\u00e4lv\u00e4l\u00e4, S., Syv\u00e4nen, V., Koistinaho, J., Luk, K.C., Lehtonen, \u0160., 2025. Human microglia reduce alpha-synuclein aggregation and are neuroprotective in adult mouse brain. Brain, Behavior, and Immunity 130, 106097. <a href=\"https:\/\/doi.org\/10.1016\/j.bbi.2025.106097\">https:\/\/doi.org\/10.1016\/j.bbi.2025.106097<\/a><\/p>\n\n\n\n<p>Niskanen, J., Peltonen, S., Ohtonen, S., Fazaludeen, M.F., Luk, K.C., Giudice, L., Koistinaho, J., Malm, T., Goldsteins, G., <strong>Albert, K<\/strong>., &amp; Lehtonen, \u0160. (2024) Uptake of alpha-synuclein preformed fibrils is suppressed by inflammation and induces an aberrant phenotype in human microglia. <em>Glia. <\/em><a href=\"https:\/\/doi.org\/10.1002\/glia.24626\">https:\/\/doi.org\/10.1002\/glia.24626<\/a><\/p>\n\n\n\n<p><strong>Albert, K<\/strong>., Goldsteins, G., K\u00e4lv\u00e4l\u00e4, S., Jolkkonen, J., &amp; Lehtonen, \u0160. (2024) Glial cell transplant for brain diseases: the supportive saviours? <em>Translational Medicine Communications<\/em>, <strong>9<\/strong>, 22. <a href=\"https:\/\/doi.org\/10.1186\/s41231-024-00182-y\">https:\/\/doi.org\/10.1186\/s41231-024-00182-y<\/a><\/p>\n\n\n\n<p><strong>Albert, K<\/strong>., K\u00e4lv\u00e4l\u00e4, S., Hakosalo, V., Syv\u00e4nen, V., Krupa, P., Niskanen, J., Peltonen, S., Sonninen, T.-M., &amp; Lehtonen, \u0160. (2022) Cellular Models of Alpha-Synuclein Aggregation: What Have We Learned and Implications for Future Study. <em>Biomedicines<\/em>, <strong>10<\/strong>, 2649.&nbsp;<a href=\"https:\/\/doi.org\/10.3390\/biomedicines10102649\">https:\/\/doi.org\/10.3390\/biomedicines10102649<\/a><\/p>\n\n\n\n<p><strong>Albert, K<\/strong>., Niskanen, J., K\u00e4lv\u00e4l\u00e4, S., &amp; Lehtonen, \u0160. (2021) Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia. <em>Int J Mol Sci<\/em>, <strong>22<\/strong>.&nbsp;<a href=\"https:\/\/doi.org\/10.3390\/ijms22094334\">https:\/\/doi.org\/10.3390\/ijms22094334<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Microglia phagocytose \u03b1-synuclein aggregates which leads to release of proinflammatory cytokines, and in contrast, we have shown that presence of these cytokines may inhibit phagocytosis of aberrant proteins by human microglia (Niskanen et al., 2024). This causes inflammatory damage to neighbouring cells, leading to fewer microglia being able to take up and degrade \u03b1-synuclein, resulting [&hellip;]<\/p>\n","protected":false},"author":1034,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-4020","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Microglia in \u03b1-synucleinopathies - Lehtonen lab\/ Human Brain Disease Modelling Research Group<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/microglia-in-\u03b1-synucleinopathies\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Microglia in \u03b1-synucleinopathies - Lehtonen lab\/ Human Brain Disease Modelling Research Group\" \/>\n<meta property=\"og:description\" content=\"Microglia phagocytose \u03b1-synuclein aggregates which leads to release of proinflammatory cytokines, and in contrast, we have shown that presence of these cytokines may inhibit phagocytosis of aberrant proteins by human microglia (Niskanen et al., 2024). This causes inflammatory damage to neighbouring cells, leading to fewer microglia being able to take up and degrade \u03b1-synuclein, resulting [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/microglia-in-\u03b1-synucleinopathies\/\" \/>\n<meta property=\"og:site_name\" content=\"Lehtonen lab\/ Human Brain Disease Modelling Research Group\" \/>\n<meta property=\"article:modified_time\" content=\"2025-10-06T08:28:09+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2025\/02\/image.png\" \/>\n\t<meta property=\"og:image:width\" content=\"1047\" \/>\n\t<meta property=\"og:image:height\" content=\"636\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/png\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/microglia-in-%ce%b1-synucleinopathies\\\/\",\"url\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/microglia-in-%ce%b1-synucleinopathies\\\/\",\"name\":\"Microglia in \u03b1-synucleinopathies - Lehtonen lab\\\/ Human Brain Disease Modelling Research Group\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/microglia-in-%ce%b1-synucleinopathies\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/microglia-in-%ce%b1-synucleinopathies\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/wp-content\\\/uploads\\\/sites\\\/286\\\/2025\\\/02\\\/image-1024x622.png\",\"datePublished\":\"2023-12-05T11:13:26+00:00\",\"dateModified\":\"2025-10-06T08:28:09+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/microglia-in-%ce%b1-synucleinopathies\\\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/microglia-in-%ce%b1-synucleinopathies\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/microglia-in-%ce%b1-synucleinopathies\\\/#primaryimage\",\"url\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/wp-content\\\/uploads\\\/sites\\\/286\\\/2025\\\/02\\\/image.png\",\"contentUrl\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/wp-content\\\/uploads\\\/sites\\\/286\\\/2025\\\/02\\\/image.png\",\"width\":1047,\"height\":636},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/microglia-in-%ce%b1-synucleinopathies\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Microglia in \u03b1-synucleinopathies\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/#website\",\"url\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/\",\"name\":\"Lehtonen lab\\\/ Human Brain Disease Modelling Research Group\",\"description\":\"\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/sites.uef.fi\\\/human-brain-disease-modelling-group\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Microglia in \u03b1-synucleinopathies - Lehtonen lab\/ Human Brain Disease Modelling Research Group","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/microglia-in-\u03b1-synucleinopathies\/","og_locale":"en_US","og_type":"article","og_title":"Microglia in \u03b1-synucleinopathies - Lehtonen lab\/ Human Brain Disease Modelling Research Group","og_description":"Microglia phagocytose \u03b1-synuclein aggregates which leads to release of proinflammatory cytokines, and in contrast, we have shown that presence of these cytokines may inhibit phagocytosis of aberrant proteins by human microglia (Niskanen et al., 2024). 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