{"id":7338,"date":"2022-05-25T13:39:07","date_gmt":"2022-05-25T04:39:07","guid":{"rendered":"https:\/\/www.med.osaka-u.ac.jp\/eng\/?page_id=7338"},"modified":"2022-08-26T14:38:47","modified_gmt":"2022-08-26T05:38:47","slug":"mochiduki2022-5-25","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2022year\/mochiduki2022-5-25","title":{"rendered":"Rika Yamashita, Goichi Beck, Hideki Mochizuki \u226aNeurology\u226b <span>A new cause of Parkinson\u2019s disease-related cell death<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li><a href=\"https:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2022year\/mochiduki2022-5-25\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><em><\/p>\n<p><span class=\"lineFrame\">Publish\u00a0<\/span> <em>Movement Disorders<\/em><\/p>\n<p><em>In an autopsy of a patient with clinically typical Parkinson\u2019s disease, researchers from Osaka University find an unexpected change in the brain: a buildup of TDP-43, rather than alpha-synuclein, proteins<\/em><\/p>\n<p class=\"figure\"><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2022\/07\/mochiduki_efig1.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-7339 size-medium\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2022\/07\/mochiduki_efig1-400x360.jpg\" alt=\"\" width=\"400\" height=\"360\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2022\/07\/mochiduki_efig1-400x360.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2022\/07\/mochiduki_efig1-768x692.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2022\/07\/mochiduki_efig1.jpg 856w\" sizes=\"(max-width: 400px) 100vw, 400px\" \/><\/a><br \/>Figure. \u00a0Schematic presentation of alpha-synuclein (1) or TDP-43 (2)-induced PD.<\/p>\n<p>There is currently no cure for Parkinson\u2019s disease (PD), and one of the main difficulties for developing treatments is that we don\u2019t know exactly how or why the disease occurs. It\u2019s generally believed that a buildup of Lewy bodies\u2014cellular inclusions that mainly contain the brain-specific protein alpha-synuclein\u2014causes cell death in key brain regions, leading to the typical symptoms of PD. However, a recent report published in <em>Movement Disorders<\/em> by researchers from Osaka University suggests that this may not be the only way in which PD-related cell death can occur.<\/p>\n<p>The report describes a patient who had what seemed to be standard PD, with no family history or disease-related gene mutations. He had typical PD motor symptoms such as rigidity, slow movement, and balance problems. He also had reduced dopamine (which helps cells talk to one another) in a brain region known as the striatum and responded well to treatment with a drug called levodopa, both of which are commonly seen in people with PD.<\/p>\n<p>After the patient\u2019s death from pneumonia, his brain was examined closely. Although it had many of the common changes that are seen in PD (such as a loss of brain cells and increased inflammation in the substantia nigra, a key PD-related brain region), some other typical changes were missing. The researchers were unable to find Lewy bodies containing alpha-synuclein in any of the regions that are normally affected in PD.<\/p>\n<p>\u201cThis was unusual,\u201d says lead author of the study Rika Yamashita. \u201cWhen we looked further, we realized that the patient had inclusions containing another type of protein: transactive response DNA-binding protein of 43 kDa, or TDP-43.\u201d<\/p>\n<p>Accumulation of TDP-43 protein occurs in other neurodegenerative diseases like amyotrophic lateral sclerosis and frontotemporal lobar degeneration, but it is not usually associated with PD. However, this new report suggests that its accumulation may cause cell loss in the substantia nigra as well as the typical motor symptoms of PD.<\/p>\n<p>\u201cThis report has implications for how we think about the development of PD,\u201d explains Goichi Beck, senior author of the report. \u201cMuch of the current research looking for PD treatments is very focused on alpha-synuclein\u2014but it may not be the only protein that causes the disease. Our findings indicate that TDP-43 accumulation may be a cause of PD separate from alpha-synuclein accumulation.\u201d<\/p>\n<p>Future studies need to take TDP-43 into consideration when investigating the mechanisms causing PD in the brain. The findings from this research suggest a new pathway for developing PD and may lead to the discovery of new treatments that slow or cure the disease, which are currently lacking.<\/p>\n<p>###<\/p>\n<p>The article, \u201cTDP-43 proteinopathy presenting with typical symptoms of Parkinson&#8217;s disease,\u201d was published in <em>Movement Disorders<\/em> at DOI: <a href=\"https:\/\/doi.org\/10.1002\/mds.29048\">https:\/\/doi.org\/10.1002\/mds.29048<\/a><\/p>\n<p><strong>Summary:<\/strong> Researchers from Osaka University have described a case of clinically typical Parkinson\u2019s disease with unusual changes in the brain. As well as the expected findings of cell loss and inflammation in disease-related brain regions, there were accumulations of the protein TDP-43 instead of the usual alpha-synuclein inclusions. This report suggests that TDP-43 accumulation can cause Parkinson\u2019s disease-like symptoms and brain changes, which may be important for developing new treatments for this currently uncurable disease.<\/p>\n<p><strong>Tweet 1:<\/strong> An unusual case of Parkinson\u2019s disease challenges our understanding of how the disease develops and may lead to better treatments<\/p>\n<p><strong>Tweet 2:<\/strong> A new possible cause of cell death in Parkinson\u2019s disease may unlock new treatment avenues, say researchers from Osaka University<\/p>\n<p><strong>Primary Keyword:<\/strong> \u00a0Health and medicine<br \/><strong>Additional Keywords:<\/strong>Parkinsons disease, Neurodegenerative diseases, Clinical Neuroscience, Clinical medicine, Cell death<\/p>\n<p><strong>Method of Research:<\/strong> Case study<\/p>\n<p><strong>Subject of Research:<\/strong>Human tissue samples<\/p>\n<p>Title: \u201cTDP-43 proteinopathy presenting with typical symptoms of Parkinson\u2019s disease\u201d<br \/>Journal: <em>Movement Disorders<\/em><em><br \/><\/em>Authors: Rika Yamashita, Goichi Beck, Yuki Yonenobu, Kimiko Inoue, Akihiko Mitsutake, Hiroyuki Ishiura, Masato Hasegawa, Shigeo Murayama, and Hideki Mochizuki<br \/>DOI: <a href=\"https:\/\/doi.org\/10.1002\/mds.29048\">10.1002\/mds.29048<\/a><\/p>\n<p>Funded by: Japan Society for the Promotion of Science, Japan Agency for Medical Research and Development<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Publish\u00a0 Movement Disorders In an autopsy of a patient with clinically typical Parkinson\u2019s di [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":7339,"parent":6951,"menu_order":162,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/7338"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=7338"}],"version-history":[{"count":5,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/7338\/revisions"}],"predecessor-version":[{"id":7561,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/7338\/revisions\/7561"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/6951"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/7339"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=7338"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}