{"id":110335,"date":"2024-10-04T14:56:50","date_gmt":"2024-10-04T07:56:50","guid":{"rendered":"https:\/\/hotvideos24.online\/?p=110335"},"modified":"2024-10-04T14:56:50","modified_gmt":"2024-10-04T07:56:50","slug":"dual-targeting-drug-halts-tau-accumulation-in-alzheimers","status":"publish","type":"post","link":"https:\/\/hotvideos24.online\/?p=110335","title":{"rendered":"Dual-Targeting Drug Halts Tau Accumulation in Alzheimer&#8217;s"},"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>Scientists have developed a drug that targets both major aggregation-promoting sites of the Tau protein, a key player in Alzheimer\u2019s disease. This peptide inhibitor, RI-AG03, effectively prevents Tau buildup in lab studies and fruit flies, offering hope for new Alzheimer\u2019s treatments.<\/p>\n<p>Unlike current drugs, RI-AG03 uniquely blocks both Tau \u201chotspots,\u201d potentially leading to safer, more targeted therapies. Researchers plan to test the drug in rodents before advancing to clinical trials.<\/p>\n<p><strong>Key Facts<\/strong>:<\/p>\n<ul class=\"wp-block-list\">\n<li>RI-AG03 blocks Tau protein buildup, preventing neurodegeneration.<\/li>\n<li>It targets both major Tau \u201chotspots\u201d for aggregation, a novel approach.<\/li>\n<li>The drug extended the lifespan of fruit fly models of Alzheimer\u2019s disease.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>University of Southampton<\/p>\n<p><strong>An international team of researchers have made a promising breakthrough in the development of drugs to treat Alzheimer\u2019s Disease.<\/strong><\/p>\n<p>For the first time, scientists have developed a drug that works on both major aggregation-promoting \u2018hotspots\u2019 of the Tau protein \u2013 addressing a critical gap in current treatments.<\/p>\n<p>The drug, a peptide inhibitor called RI-AG03, was effective at preventing the build-up of Tau proteins \u2013 a key driver of neurodegeneration \u2013 in both lab and fruit fly studies.<\/p>\n<figure class=\"wp-block-image size-full\"><picture fetchpriority=\"high\" decoding=\"async\" class=\"wp-image-105063\"><source type=\"image\/webp\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience.jpg.webp 1200w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-300x200.jpg.webp 300w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-770x513.jpg.webp 770w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-1155x770.jpg.webp 1155w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-370x247.jpg.webp 370w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-293x195.jpg.webp 293w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-150x100.jpg.webp 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/><img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"800\" src=\"https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience.jpg\" alt=\"This shows neurons.\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience.jpg 1200w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-300x200.jpg 300w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-770x513.jpg 770w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-1155x770.jpg 1155w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-370x247.jpg 370w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-293x195.jpg 293w, https:\/\/neurosciencenews.com\/files\/2024\/10\/tau-drug-alzheimers-neuroscience-150x100.jpg 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/> <\/picture><figcaption class=\"wp-element-caption\">Here too, they found the drug successfully penetrated the cells and reduced the aggregation of Tau proteins. Credit: Neuroscience News<\/figcaption><\/figure>\n<p>The research, published today [3<sup>\u00a0<\/sup>October 2024] in\u00a0<em>Alzheimer\u2019s &amp; Dementia: The Journal of the Alzheimer\u2019s Association,<\/em>\u00a0was undertaken by the University of Southampton in collaboration with Lancaster University, Nottingham Trent University, Tokyo Metropolitan Institute of Medical Science and UT Southwestern Medical Centre.<\/p>\n<p>Dr Anthony Aggidis, lead author of the paper, Visiting Researcher at the University of Southampton and former Postdoctoral Research Associate at Lancaster University said: \u201cOur research represents an important step toward creating treatments that can prevent the progression of diseases like Alzheimer\u2019s disease.<\/p>\n<p>\u201cBy targeting both of the key areas on the Tau protein, this unique approach could help address the growing impact of dementia on society, providing a much-needed new option for treating these devastating diseases.\u201d<\/p>\n<p><strong>A significant breakthrough<\/strong><\/p>\n<p>Tau proteins play a crucial role in maintaining the structure and function of neurons (brain cells). But in Alzheimer\u2019s disease, these proteins malfunction, clumping together to form long, twisting fibrils.<\/p>\n<p>As the fibrils accumulate, they create what are called neurofibrillary tangles \u2013 masses of twisted Tau proteins that clog the neurons, preventing them from getting the nutrients and signals they need to survive.<\/p>\n<p>As more neurons die, memory, thinking, and behaviour become increasingly impaired, leading to the cognitive decline seen in Alzheimer\u2019s.<\/p>\n<p>There are two specific \u2018hotspots\u2019 of the Tau protein where this clumping tends to happen. While current treatments target one or the other of these hotspots, RI-AG03 uniquely targets and blocks both.<\/p>\n<p>\u201cThere are two regions of the Tau protein that act like a zipper to enable it to aggregate,\u201d says Amritpal Mudher, Professor of Neuroscience at the University of Southampton and one of the lead authors on the paper.<\/p>\n<p>\u201cFor the first time, we have a drug which is effective in inhibiting both these regions. This dual-targeting mechanism is significant because it addresses both domains that stimulate Tau aggregation, potentially paving the way for more effective treatments for neurodegenerative diseases like Alzheimer\u2019s.\u201d<\/p>\n<p><strong>Targeted approach<\/strong><\/p>\n<p>The peptide-based approach is also more targeted than current treatments, potentially making it safer, with fewer side effects.<\/p>\n<p>\u201cWe know that the toxicity of the Tau protein is intimately linked with its ability to aggregate, so by inhibiting aggregation we expect to see desirable effects,\u201d says Dr Aggidis.<\/p>\n<p>\u201cBut current aggregation inhibitors have had many side effects because they can interfere with the functions of many other proteins.<\/p>\n<p>\u201cRI-AG03 is specifically designed against the Tau protein, meaning it\u2019s less likely to undesirably interact with other proteins.\u201d<\/p>\n<p><strong>Testing RI-AG03<\/strong><\/p>\n<p>The paper describes how RI-AG03 was first developed by Dr Aggidis, in the laboratory of the late Prof David Allsop, using computational biology at Lancaster University, where it was tested in lab dishes.<\/p>\n<p>To test its effectiveness in cells within a living organism, researchers at the University of Southampton then gave the drug to fruit flies that had pathogenic Tau. These fruit fly models of Alzheimer\u2019s Disease were generated by Dr Shreyasi Chatterjee who is a Senior Lecturer at Nottingham Trent University.<\/p>\n<p>The researchers found the drug suppressed neurodegeneration and extended the lives of the flies by around two weeks \u2013 a significant extension considering the life span of the insects.<\/p>\n<p>To understand what was happening, Southampton\u2019s scientists looked deep into the brains of the fruit flies.<\/p>\n<p>Prof Mudher said: \u201cWhen we didn\u2019t feed the flies with the peptide inhibitor, they had lots of the pathogenic fibrils, which group together to make up a tangle. But when we fed them with the drug, the pathogenic fibrils decreased significantly in quantity.\u201d<\/p>\n<p>\u201cThe higher the dosage given, the greater the improvement we saw in the fruit fly\u2019s lifespan.\u201d<\/p>\n<p>To make sure this wasn\u2019t unique to fruit flies, researchers at UT Southwestern Medical Centre tested the drug in a biosensor cell \u2013 a type of living human cell line that is engineered to detect pathogenic tau fibril formation.<\/p>\n<p>Here too, they found the drug successfully penetrated the cells and reduced the aggregation of Tau proteins.<\/p>\n<p>The team believe their work will have a significant impact on drug discovery efforts in the field of neurodegenerative diseases and now plans to test RI-AG03 in rodents, before proceeding to clinical trials.<\/p>\n<p>The research was funded by the Alzheimer\u2019s Society. Dr Richard Oakley, Associate Director of Research and Innovation, said:\u00a0\u201cDementia is the UK\u2019s biggest killer, and it applies enormous cost and pressure to our healthcare system which is why we\u2019re committed to funding world leading studies like this one. \u00a0<\/p>\n<p>\u201cThis research is taking promising steps towards a new one-of-a-kind therapy which targets Tau, a damaging protein in the brains of people living with Alzheimer\u2019s, preventing it from clumping together. This drug has the potential to be more targeted than others currently being studied, and we hope it will result in fewer toxic side effects. \u00a0<\/p>\n<p>\u201cIt\u2019s important to note that the study is in its early stages, so we don\u2019t yet know if it will work or be safe for humans, but it\u2019s an exciting development and we look forward to seeing where it leads.\u00a0<\/p>\n<p>\u201cResearch will beat dementia, but we need to make it a reality sooner through more funding, more partnerships, and more people taking part in dementia research. To find out about Alzheimer\u2019s Society research or to take part visit <a href=\"https:\/\/alzheimers.org.uk\/research\" target=\"_blank\" rel=\"noreferrer noopener\">alzheimers.org.uk\/research<\/a>.\u201d\u00a0<\/p>\n<h2 class=\"wp-block-heading\">About this neuropharmacology and Alzheimer\u2019s disease 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#e79493829182c9908e8b8b8e868a94a79488938889c98684c9928c\" target=\"_blank\" rel=\"noreferrer noopener\">Steven Williams<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/soton.ac.uk\" target=\"_blank\" rel=\"noreferrer noopener\">University of Southampton<\/a><br \/><strong>Contact: <\/strong>Steven Williams \u2013 University of Southampton<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:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.14246\" target=\"_blank\" rel=\"noreferrer noopener\">A novel peptide-based tau aggregation inhibitor as a potential therapeutic for Alzheimer\u2019s disease and other tauopathies<\/a>\u201d by Anthony Aggidis et al. <em>Alzheimer\u2019s &amp; Dementia<\/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>A novel peptide-based tau aggregation inhibitor as a potential therapeutic for Alzheimer\u2019s disease and other tauopathies<\/strong><\/p>\n<h3 class=\"wp-block-heading\" id=\"alz14246-sec-0010-title\">INTRODUCTION<\/h3>\n<p>As aggregation underpins Tau toxicity, aggregation inhibitor peptides may have disease-modifying potential. They are therefore currently being designed and target either the\u00a0<sup>306<\/sup>VQIVYK<sup>311<\/sup>\u00a0aggregation-promoting hotspot found in all Tau isoforms or the\u00a0<sup>275<\/sup>VQIINK<sup>280<\/sup>\u00a0aggregation-promoting hotspot found in 4R isoforms. However, for any Tau aggregation inhibitor to potentially be clinically relevant for other tauopathies, it should target both hotspots to suppress aggregation of Tau isoforms, be stable, cross the blood-brain barrier, and rescue aggregation-dependent Tau phenotypes in vivo.<\/p>\n<h3 class=\"wp-block-heading\" id=\"alz14246-sec-0020-title\">METHODS<\/h3>\n<p>We developed a retro-inverso, stable D-amino peptide, RI-AG03 [Ac-rrrrrrrrGpkyk(ac)iqvGr-NH2], based on the\u00a0<sup>306<\/sup>VQIVYK<sup>311<\/sup>\u00a0hotspots which exhibit these disease-relevant attributes.<\/p>\n<h3 class=\"wp-block-heading\" id=\"alz14246-sec-0030-title\">RESULTS<\/h3>\n<p>Unlike other aggregation inhibitors, RI-AG03 effectively suppresses aggregation of multiple Tau species containing both hotspots in vitro and in vivo, is non-toxic, and suppresses aggregation-dependent neurodegenerative and behavioral phenotypes.<\/p>\n<h3 class=\"wp-block-heading\" id=\"alz14246-sec-0040-title\">DISCUSSION<\/h3>\n<p>RI-AG03 therefore meets many clinically relevant requirements for an anti-aggregation Tau therapeutic and should be explored further for its disease-modifying potential for Tauopathies.<\/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\/tau-drug-alzheimers-neurology-27775\/\">Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Summary: Scientists have developed a drug that targets both major aggregation-promoting sites of the Tau protein, a key player in Alzheimer\u2019s disease. This peptide inhibitor, RI-AG03, effectively prevents Tau buildup &hellip; <a href=\"https:\/\/hotvideos24.online\/?p=110335\" 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-110335","post","type-post","status-publish","format-standard","hentry","category-health","entry"],"_links":{"self":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/posts\/110335","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=110335"}],"version-history":[{"count":0,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/posts\/110335\/revisions"}],"wp:attachment":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=110335"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=110335"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=110335"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}