{"id":125538,"date":"2024-11-14T00:27:52","date_gmt":"2024-11-13T17:27:52","guid":{"rendered":"https:\/\/hotvideos24.online\/?p=125538"},"modified":"2024-11-14T00:27:52","modified_gmt":"2024-11-13T17:27:52","slug":"parkinsons-progression-linked-to-new-protein-pathway","status":"publish","type":"post","link":"https:\/\/hotvideos24.online\/?p=125538","title":{"rendered":"Parkinson\u2019s Progression Linked to New Protein Pathway"},"content":{"rendered":"<p> <script async src=\"https:\/\/pagead2.googlesyndication.com\/pagead\/js\/adsbygoogle.js?client=ca-pub-3711241968723425\"\r\n     crossorigin=\"anonymous\"><\/script>\r\n<ins class=\"adsbygoogle\"\r\n     style=\"display:block\"\r\n     data-ad-format=\"fluid\"\r\n     data-ad-layout-key=\"-fb+5w+4e-db+86\"\r\n     data-ad-client=\"ca-pub-3711241968723425\"\r\n     data-ad-slot=\"7910942971\"><\/ins>\r\n<script>\r\n     (adsbygoogle = window.adsbygoogle || []).push({});\r\n<\/script><br \/>\n<\/p>\n<div>\n<p><strong>Summary: <\/strong>Researchers have identified a protein, TMEM16F, that appears to aid the spread of Parkinson\u2019s pathology in the brain. They found that a mutation in this protein promotes the secretion of a harmful form of \u03b1-synuclein, which moves through nerve cells, forming toxic Lewy bodies.<\/p>\n<p>Mice without the TMEM16F gene showed reduced spread of Parkinson\u2019s pathology, suggesting this protein as a potential therapeutic target. The mutation, common among Ashkenazi Jews, could provide insights into genetic risk factors and future interventions. By possibly inhibiting TMEM16F, researchers hope to slow the spread of Parkinson\u2019s.<\/p>\n<p><strong>Key Facts:<\/strong><\/p>\n<ul class=\"wp-block-list\">\n<li>TMEM16F mutation increases secretion of toxic \u03b1-synuclein, accelerating Parkinson\u2019s spread.<\/li>\n<li>Mice lacking TMEM16F showed reduced \u03b1-synuclein pathology spread.<\/li>\n<li>Findings suggest TMEM16F as a target for potential Parkinson\u2019s treatments.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>Tel Aviv University<\/p>\n<p><strong>Researchers at Tel Aviv University (TAU) discovered a new factor in the pathology of Parkinson\u2019s disease, which in the future may serve as a target for developing new treatments for this terrible ailment, affecting close to 10 million people worldwide. <\/strong><\/p>\n<p>The researchers: \u201cWe found that a variant of the TMEM16F protein, caused by a genetic mutation, enhances the spread of Parkinson\u2019s pathology through nerve cells in the brain.\u201d<\/p>\n<figure class=\"wp-block-image size-full\"><picture fetchpriority=\"high\" decoding=\"async\" class=\"wp-image-106126\"><source type=\"image\/webp\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence.jpg.webp 1200w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-300x200.jpg.webp 300w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-770x513.jpg.webp 770w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-1155x770.jpg.webp 1155w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-370x247.jpg.webp 370w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-293x195.jpg.webp 293w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-150x100.jpg.webp 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/><img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"799\" src=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence.jpg\" alt=\"This shows DNA.\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence.jpg 1200w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-300x200.jpg 300w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-770x513.jpg 770w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-1155x770.jpg 1155w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-370x247.jpg 370w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-293x195.jpg 293w, https:\/\/neurosciencenews.com\/files\/2024\/11\/parkinsons-genetic-pathway-neurosicence-150x100.jpg 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/> <\/picture><figcaption class=\"wp-element-caption\">They found that when the TMEM16F gene had been deleted, the \u03b1-synuclein pathology spread to fewer healthy neighboring cells compared to the spread from normal cells. Credit: Neuroscience News<\/figcaption><\/figure>\n<p>The study was led by Dr. Avraham Ashkenazi and PhD student Stav Cohen Adiv Mordechai from the Department of Cell and Developmental Biology at TAU\u2019s Faculty of Medical and Health Sciences and the Sagol School of Neuroscience. Other contributors included: Dr. Orly Goldstein, Prof. Avi Orr-Urtreger, Prof. Tanya Gurevich and Prof. Nir Giladi from TAU\u2019s Faculty of Medical and Health Sciences and the Tel Aviv Sourasky Medical Center, as well as other researchers from TAU and the University of Haifa. The study was backed by the Aufzien Family Center for the Prevention and Treatment of Parkinson\u2019s Disease at TAU.<\/p>\n<p>The paper was published in the scientific journal\u00a0<em>Aging Cell.<\/em><\/p>\n<p>Doctoral student Stav Cohen Adiv Mordechai explains: \u201cA key mechanism of Parkinson\u2019s disease is the aggregation in brain cells of the protein\u00a0\u03b1-synuclein\u00a0(in the form of Lewy bodies), eventually killing these cells.<\/p>\n<p>\u201cFor many years researchers have tried to discover how the pathological version of \u03b1-synuclein spreads through the brain, affecting one cell after another, and gradually destroying whole sections of the brain.<\/p>\n<p>\u201cSince \u03b1-synuclein needs to cross the cell membrane in order to spread, we focused on the protein TMEM16F, a regulator situated in the cell membrane, as a possible driver of this lethal process.\u201d<\/p>\n<p>At first, the researchers genetically engineered a mouse model without the TMEM16F gene, and derived neurons from the brains of these mice for an\u00a0<em>in-vitro<\/em>\u00a0cellular model. Using a specially engineered virus, they caused these neurons to express the defective\u00a0\u03b1-synuclein\u00a0associated with Parkinson\u2019s and compared the results with outcomes from normal brain cells containing TMEM16F.<\/p>\n<p>They found that when the TMEM16F gene had been deleted, the \u03b1-synuclein pathology spread to fewer healthy neighboring cells compared to the spread from normal cells. The results were validated\u00a0<em>in-vivo<\/em>\u00a0in a living mouse model of Parkinson\u2019s disease.<\/p>\n<p>In addition, in collaboration with the Neurological Institute at the Tel Aviv Sourasky Medical Center, the researchers looked for mutations (variants) in the TMEM16F gene that might increase the risk for Parkinson\u2019s disease.<\/p>\n<p>Dr. Ashkenazi explains: \u201cThe incidence of Parkinson\u2019s among Ashkenazi Jews is known to be relatively high, and the Institute conducts a vast ongoing genetic study on Ashkenazi Jews who carry genes increasing the risk for the disease. With their help, we were able to identify a specific TMEM16F mutation which is common in Ashkenazi Jews in general, and in Ashkenazi Parkinson\u2019s patients in particular.\u201d<\/p>\n<p>Cells carrying the mutation were found to secrete more pathological \u03b1-synuclein compared to cells with the normal gene. The researchers explain that the mechanism behind increased secretion has to do with the biological function of the TMEM16F protein: the mutation increases the activity of TMEM16F, thereby affecting membrane secretion processes.<\/p>\n<p>Stav Cohen Adiv Mordechai: \u201cIn our study, we discovered a new factor underlying Parkinson\u2019s disease: the protein TMEM16F, which mediates secretion of the pathological \u03b1-synuclein protein through the cell membrane to the cell environment.<\/p>\n<p>\u201cPicked up by healthy neurons nearby, the defective \u03b1-synuclein forms Lewy bodies inside them, and gradually spreads through the brain, damaging more and more brain cells. Our findings mark TMEM16F as a possible new target for the development of effective treatments for Parkinson\u2019s disease.<\/p>\n<p>\u201cIf, by inhibiting TMEM16F, we can stop or reduce the secretion of defective \u03b1-synuclein from brain cells, we may be able to slow down or even halt the spread of the disease through the brain.\u201d<\/p>\n<p>Dr. Ashkenazi emphasizes that research on the new Parkinson\u2019s mechanism has only begun, and quite a number of questions still remain to be explored: Does inhibiting TMEM16F actually reduce the symptoms of Parkinson\u2019s disease? Does the lipid composition of cell membranes play a part in the spread of the disease in the brain? Is there a link between mutations in TMEM16F and the prevalence of Parkinson\u2019s in the population?<\/p>\n<p>The research team intends to continue the investigation in these directions and more.<\/p>\n<h2 class=\"wp-block-heading\">About this Parkinson\u2019s disease and genetics research news<\/h2>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author: <\/strong><a href=\"http:\/\/neurosciencenews.com\/cdn-cgi\/l\/email-protection#66320713161426120713031e48120713480705480f0a\" target=\"_blank\" rel=\"noreferrer noopener\">Noga Shahar<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/tau.ac.il\" target=\"_blank\" rel=\"noreferrer noopener\">Tel Aviv University<\/a><br \/><strong>Contact: <\/strong>Noga Shahar \u2013 Tel Aviv University<br \/><strong>Image: <\/strong>The image is credited to Neuroscience News<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Original Research: <\/strong>Open access.<br \/>\u201c<a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1111\/acel.14387\" target=\"_blank\" rel=\"noreferrer noopener\">TMEM16F regulates pathologic \u03b1-synuclein secretion and spread in cellular and mouse models of Parkinson\u2019s disease<\/a>\u201d by Avraham Ashkenazi et al. <em>Aging Cell<\/em><\/p>\n<hr class=\"wp-block-separator has-text-color has-pale-cyan-blue-color has-alpha-channel-opacity has-pale-cyan-blue-background-color has-background\"\/>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>TMEM16F regulates pathologic \u03b1-synuclein secretion and spread in cellular and mouse models of Parkinson\u2019s disease<\/strong><\/p>\n<p>One of the main hallmarks of Parkinson\u2019s disease (PD) pathology is the spread of the aggregate-prone protein \u03b1-synuclein (\u03b1-syn), which can be detected in the plasma and cerebrospinal fluid of patients as well as in the extracellular environment of neuronal cells.<\/p>\n<p>The secreted \u03b1-syn can exhibit \u201cprion-like\u201d behavior and transmission to na\u00efve cells can promote conformational changes and pathology. The precise role of plasma membrane proteins in the pathologic process of \u03b1-syn is yet to be fully resolved.<\/p>\n<p>The TMEM16 family of lipid scramblases and ion channels has been recently associated with cancer and infectious diseases but is less known for its role in aging-related diseases.<\/p>\n<p>To elucidate the role of TMEM16F in \u03b1-syn spread, we transduced neurons derived from TMEM16F knockout mice with a reporter system that enables the distinction between donor and recipient neurons of pathologic \u03b1-synA53T.<\/p>\n<p>We found that the spread of \u03b1-synA53T was reduced in neurons derived from TMEM16F-knockout mice. These findings were recapitulated in\u00a0vivo in a mouse model of PD, where attenuated \u03b1-synA53T spread was observed when TMEM16F was ablated.<\/p>\n<p>Moreover, we identified a single nucleotide polymorphism in TMEM16F of Ashkenazi Jewish PD patients resulting in a missense Ala703Ser mutation with enhanced lipid scramblase activity.<\/p>\n<p>This mutation is associated with altered regulation of \u03b1-synA53T extracellular secretion in cellular models of PD.<\/p>\n<p>Our study highlights TMEM16F as a novel regulator of \u03b1-syn spread and as a potential therapeutic target in synucleinopathies.<\/p>\n<p> <!-- Form created by Optin Forms plugin by WPKube: create beautiful optin forms with ease! --> <!-- https:\/\/wpkube.com\/ --><!--optinforms-form5-container--> <!-- \/ Optin Forms --> <\/div>\n<p><script async src=\"https:\/\/pagead2.googlesyndication.com\/pagead\/js\/adsbygoogle.js?client=ca-pub-3711241968723425\"\r\n     crossorigin=\"anonymous\"><\/script>\r\n<ins class=\"adsbygoogle\"\r\n     style=\"display:block\"\r\n     data-ad-format=\"fluid\"\r\n     data-ad-layout-key=\"-fb+5w+4e-db+86\"\r\n     data-ad-client=\"ca-pub-3711241968723425\"\r\n     data-ad-slot=\"7910942971\"><\/ins>\r\n<script>\r\n     (adsbygoogle = window.adsbygoogle || []).push({});\r\n<\/script><br \/>\n<br \/><div data-type=\"_mgwidget\" data-widget-id=\"1660802\">\r\n<\/div>\r\n<script>(function(w,q){w[q]=w[q]||[];w[q].push([\"_mgc.load\"])})(window,\"_mgq\");\r\n<\/script>\r\n<br \/>\n<br \/><a href=\"https:\/\/neurosciencenews.com\/parkinsons-tmem16f-pathway-28035\/\">Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Summary: Researchers have identified a protein, TMEM16F, that appears to aid the spread of Parkinson\u2019s pathology in the brain. They found that a mutation in this protein promotes the secretion &hellip; <a href=\"https:\/\/hotvideos24.online\/?p=125538\" class=\"more-link\">Read More<\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[],"class_list":["post-125538","post","type-post","status-publish","format-standard","hentry","category-health","entry"],"_links":{"self":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/posts\/125538","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=125538"}],"version-history":[{"count":0,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/posts\/125538\/revisions"}],"wp:attachment":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=125538"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=125538"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=125538"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}