{"id":491,"date":"2021-05-18T11:25:34","date_gmt":"2021-05-18T08:25:34","guid":{"rendered":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/?page_id=491"},"modified":"2023-10-12T10:57:50","modified_gmt":"2023-10-12T07:57:50","slug":"lewy-bodies-and-dopaminergic-neurons","status":"publish","type":"page","link":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/","title":{"rendered":""},"content":{"rendered":"\n

<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n
\n
\n
\"\"
ICC-F Tyrosine hydroxylase staining visualizing hiPSC derived dopaminergic neurons<\/figcaption><\/figure>\n\n\n\n
\"\"
ICC-F TUJ1 staining visualizing intracellular neuronal tubules structures and neuronal network<\/figcaption><\/figure>\n\n\n\n
\"\"
Overlapping fluorescence channel image<\/figcaption><\/figure>\n<\/div>\n\n\n\n
\n

Lewy body-like inclusions are modelled routinely using either by a overexpression of \u03b1-synuclein (\u03b1Syn) coding SNCA or by inducing pre-formed fibrills (PFFs) of short length alpha-synuclein fibrils (1). Previously it has been shown that, while SNCA is a risk factor for causing Parkinson’s disease (PD) and it is an classical example for familial PD with \u03b1Syn aggregations, its expression levels, which could be controlled by the methylation status of the gene, might not to be increased in the sporadic PD cases (2), while controversy remains (3). <\/p>\n\n\n\n

We aim to produce more authentic Lewy body-like inclusions by cultivating for longer periods of time after inducing with \u03b1Syn PFFs and in the correct conditions. We aim to see multicellular fractions as reported in PD (4). We aim to produce robust Lewy body pathology without the SNCA overexpression in a correct cultivation method, similar to Tanudjojo et al. (5). For this model we will conduct an accurate genetic screening and further dissect the disease pathway in mono- and co-cultures.<\/p>\n<\/div>\n<\/div>\n\n\n\n

    \n
  1. Luk, K. C. et al. (2009) \u2018Exogenous \u03b1-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells\u2019, Proceedings of the National Academy of Sciences of the United States of America, 106(47), pp. 20051\u201320056. doi: 10.1073\/pnas.0908005106.<\/li>\n\n\n\n
  2. Guhathakurta, S. et al. (2017) \u2018Hypomethylation of intron1 of \u03b1-synuclein gene does not correlate with Parkinson\u2019s disease\u2019, Molecular Brain, 10(1), p. 6. doi: 10.1186\/s13041-017-0285-z.<\/li>\n\n\n\n
  3. Jowaed, A. et al. (2010) \u2018Methylation Regulates Alpha-Synuclein Expression and Is Decreased in Parkinson\u2019s Disease Patients\u2019 Brains\u2019, Journal of Neuroscience, 30(18), pp. 6355\u20136359. doi: 10.1523\/JNEUROSCI.6119-09.2010.<\/li>\n\n\n\n
  4. Shahmoradian, S. H. et al. (2019) \u2018Lewy pathology in Parkinson\u2019s disease consists of crowded organelles and lipid membranes\u2019, Nature Neuroscience, 22(7), pp. 1099\u20131109. doi: 10.1038\/s41593-019-0423-2.<\/li>\n\n\n\n
  5. Tanudjojo, B. et al. (2021) \u2018Phenotypic manifestation of \u03b1-synuclein strains derived from Parkinson\u2019s disease and multiple system atrophy in human dopaminergic neurons\u2019, Nature Communications, 12(1), p. 3817. doi: 10.1038\/s41467-021-23682-z.<\/li>\n<\/ol>\n\n\n\n

    <\/p>\n","protected":false},"excerpt":{"rendered":"

    Lewy body-like inclusions are modelled routinely using either by a overexpression of \u03b1-synuclein (\u03b1Syn) coding SNCA or by inducing pre-formed fibrills (PFFs) of short length alpha-synuclein fibrils (1). Previously it has been shown that, while SNCA is a risk factor for causing Parkinson’s disease (PD) and it is an classical example for familial PD with […]<\/p>\n","protected":false},"author":575,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-491","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"\n- 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\/lewy-bodies-and-dopaminergic-neurons\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"- Lehtonen lab\/ Human Brain Disease Modelling Research Group\" \/>\n<meta property=\"og:description\" content=\"Lewy body-like inclusions are modelled routinely using either by a overexpression of \u03b1-synuclein (\u03b1Syn) coding SNCA or by inducing pre-formed fibrills (PFFs) of short length alpha-synuclein fibrils (1). Previously it has been shown that, while SNCA is a risk factor for causing Parkinson’s disease (PD) and it is an classical example for familial PD with […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/\" \/>\n<meta property=\"og:site_name\" content=\"Lehtonen lab\/ Human Brain Disease Modelling Research Group\" \/>\n<meta property=\"article:modified_time\" content=\"2023-10-12T07:57:50+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2023\/10\/GraphA-biorender-121023_ViliH-1024x754.png\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"3 minutes\" \/>\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\/lewy-bodies-and-dopaminergic-neurons\/\",\"url\":\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/\",\"name\":\"- 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\/lewy-bodies-and-dopaminergic-neurons\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2023\/10\/GraphA-biorender-121023_ViliH-1024x754.png\",\"datePublished\":\"2021-05-18T08:25:34+00:00\",\"dateModified\":\"2023-10-12T07:57:50+00:00\",\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/#primaryimage\",\"url\":\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2023\/10\/GraphA-biorender-121023_ViliH.png\",\"contentUrl\":\"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2023\/10\/GraphA-biorender-121023_ViliH.png\",\"width\":3000,\"height\":2209},{\"@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":"- 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\/lewy-bodies-and-dopaminergic-neurons\/","og_locale":"en_US","og_type":"article","og_title":"- Lehtonen lab\/ Human Brain Disease Modelling Research Group","og_description":"Lewy body-like inclusions are modelled routinely using either by a overexpression of \u03b1-synuclein (\u03b1Syn) coding SNCA or by inducing pre-formed fibrills (PFFs) of short length alpha-synuclein fibrils (1). Previously it has been shown that, while SNCA is a risk factor for causing Parkinson’s disease (PD) and it is an classical example for familial PD with […]","og_url":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/","og_site_name":"Lehtonen lab\/ Human Brain Disease Modelling Research Group","article_modified_time":"2023-10-12T07:57:50+00:00","og_image":[{"url":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2023\/10\/GraphA-biorender-121023_ViliH-1024x754.png","type":"","width":"","height":""}],"twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"3 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/","url":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/","name":"- 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\/lewy-bodies-and-dopaminergic-neurons\/#primaryimage"},"image":{"@id":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/#primaryimage"},"thumbnailUrl":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2023\/10\/GraphA-biorender-121023_ViliH-1024x754.png","datePublished":"2021-05-18T08:25:34+00:00","dateModified":"2023-10-12T07:57:50+00:00","inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/"]}]},{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/lewy-bodies-and-dopaminergic-neurons\/#primaryimage","url":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2023\/10\/GraphA-biorender-121023_ViliH.png","contentUrl":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-content\/uploads\/sites\/286\/2023\/10\/GraphA-biorender-121023_ViliH.png","width":3000,"height":2209},{"@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"}]}},"_links":{"self":[{"href":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-json\/wp\/v2\/pages\/491","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-json\/wp\/v2\/users\/575"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-json\/wp\/v2\/comments?post=491"}],"version-history":[{"count":2,"href":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-json\/wp\/v2\/pages\/491\/revisions"}],"predecessor-version":[{"id":3635,"href":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-json\/wp\/v2\/pages\/491\/revisions\/3635"}],"wp:attachment":[{"href":"https:\/\/sites.uef.fi\/human-brain-disease-modelling-group\/wp-json\/wp\/v2\/media?parent=491"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}