{"id":115821,"date":"2024-10-19T04:52:07","date_gmt":"2024-10-18T21:52:07","guid":{"rendered":"https:\/\/hotvideos24.online\/?p=115821"},"modified":"2024-10-19T04:52:07","modified_gmt":"2024-10-18T21:52:07","slug":"how-a-brain-lipids-production-could-impact-dementia","status":"publish","type":"post","link":"https:\/\/hotvideos24.online\/?p=115821","title":{"rendered":"How a Brain Lipid&#8217;s Production Could Impact Dementia"},"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 discovered how a lipid molecule, BMP, crucial for brain function, is produced, potentially opening new doors for treating neurodegenerative diseases like Alzheimer\u2019s and frontotemporal dementia. Two enzymes, PLD3 and PLD4, were found to catalyze the formation of BMP by changing the molecule\u2019s \u201chandedness,\u201d allowing it to remain stable in lysosomes where other lipids are broken down.<\/p>\n<p>This finding sheds light on lipid regulation in the brain, helping to explain the buildup of toxic molecules in conditions like dementia. The research offers a promising new direction for understanding brain health and developing future therapies.<\/p>\n<p><strong>Key Facts:<\/strong><\/p>\n<ul class=\"wp-block-list\">\n<li>BMP, a lipid vital for brain health, is produced by PLD3 and PLD4 enzymes.<\/li>\n<li>These enzymes change BMP\u2019s \u201chandedness,\u201d allowing it to stabilize in lysosomes.<\/li>\n<li>Understanding BMP production could lead to therapies for Alzheimer\u2019s and dementia.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>HHMI<\/p>\n<p><strong>Scientists have gained a deeper understanding of a molecule that regulates lipid levels in the brain. This breakthrough could eventually lead to treatments for diseases like frontotemporal dementia and Alzheimer\u2019s disease. <\/strong><\/p>\n<p>The findings are\u00a0published\u00a0in the journal\u00a0<em>Cell<\/em>.<\/p>\n<p>How do you make a fatty molecule that is involved in breaking down other fats in the brain, yet doesn\u2019t get destroyed itself? It\u2019s a question that has wracked scientists\u2019 brains for half a century.<\/p>\n<figure class=\"wp-block-image size-full\"><picture fetchpriority=\"high\" decoding=\"async\" class=\"wp-image-105529\"><source type=\"image\/webp\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence.jpg.webp 1200w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-300x200.jpg.webp 300w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-770x513.jpg.webp 770w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-1155x770.jpg.webp 1155w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-370x247.jpg.webp 370w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-293x195.jpg.webp 293w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-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\/brain-lipid-dementia-neurosicence.jpg\" alt=\"This shows a brain.\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence.jpg 1200w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-300x200.jpg 300w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-770x513.jpg 770w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-1155x770.jpg 1155w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-370x247.jpg 370w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-293x195.jpg 293w, https:\/\/neurosciencenews.com\/files\/2024\/10\/brain-lipid-dementia-neurosicence-150x100.jpg 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/> <\/picture><figcaption class=\"wp-element-caption\">Interestingly, PLD3 mutations that cause spinocerebellar ataxia 46, a rare neurodegenerative disease, or that increase Alzheimer\u2019s risk also reduce BMP synthesis. Credit: Neuroscience News<\/figcaption><\/figure>\n<p>BMP, or bis(monoacylglycerol)phosphate, is a phospholipid that is located in lysosomes\u2014the cell\u2019s garbage bins.<\/p>\n<p>\u201cBMP is a co-factor for degradation, but itself is very, very stable, and it has an unusual chemistry,\u201d says Howard Hughes Medical Institute Investigator Tobias Walther. \u201cAs a consequence, nobody knew how this is made.\u201d<\/p>\n<p>In the new study, Walther and Robert Farese, Jr.\u2019s team at the cell biology program of the Sloan Kettering Institute reports that two enzymes, phospholipases D3 and D4 (PLD3 and PLD4), are needed to make BMP in lab assays as well as in human cells and animal models.<\/p>\n<p>For more than 15 years, Walther and Farese\u2019s lab has investigated\u00a0frontotemporal dementia\u00a0(FTD), the disease that actor Bruce Willis was diagnosed with in 2023. It affects both the frontal and temporal lobes of the brain, which are responsible for personality, judgment, and speech.<\/p>\n<p>FTD is the most common cause of dementia in people under the age of 60, and it has no known cure or treatment.<\/p>\n<p>In previous work, the researchers discovered that FTD patients had elevated levels of gangliosides, a type of lipid that is attached to a sugar, in their brains. It turned out that these molecules were building up because of a problem with breaking them down.<\/p>\n<p>\u201cThat\u2019s when we got really interested in this BMP molecule, and we found that it was extremely low in FTD brains,\u201d says Farese.<\/p>\n<p>High levels of gangliosides are toxic, and changes in BMP activity are associated with neurodegenerative diseases, suggesting that keeping ganglioside amounts in check is important for healthy brain function.<\/p>\n<h2 class=\"wp-block-heading\">Mirror, mirror on the wall<\/h2>\n<p>As molecules go, BMP is peculiar, says Walther.<\/p>\n<p>\u201cMolecules have a pattern that is either like a left or right hand that is identical at one level, but one is a mirror image of the other,\u201d he says.<\/p>\n<p>Lipids and phospholipids are almost always in the \u201cR\u201d configuration, but BMP is one of the rare phospholipids that is in the opposite form, called \u201cS.\u201d In fact, \u201chandedness\u201d can occur in two places in BMP, and both are in the S form.<\/p>\n<p>The S handedness of BMP is what makes it so stable in the lysosome, when all of the other lipids\u2014which are R\u2014are destroyed. But the 50-year-old question is\u2014if lipids are R, how does one of them become S?<\/p>\n<p>Changing a molecule\u2019s handedness is no simple feat and it rarely occurs, says Shubham Singh, the postdoctoral fellow at the Sloan Kettering Institute who led the study.<\/p>\n<p>\u201cEverything in lipid biochemistry starts from one molecule called glycerol 3-phosphate, and it is R,\u201d says Singh.<\/p>\n<p>\u201cSo, at what step do you convert R to S, or right hand to left hand, to make BMP?\u201d<\/p>\n<h2 class=\"wp-block-heading\">Swap meet<\/h2>\n<p>Singh and colleagues observed that human cells swap, or exchange, a glycerol between two different molecules to make the S form of BMP in a reaction called transphosphatidylation.<\/p>\n<p>Then, by poring through\u00a0protein sequences\u00a0for enzymes that look like they might interact with lipids, Singh decided to test phospholipase D enzymes.<\/p>\n<p>Through a series of experiments, the researchers concluded that PLD3 and PLD4 catalyze the reaction. Bumping up PLD3 or PLD4 expression boosted BMP levels, and mutations that abolish their activity resulted in lower BMP levels.<\/p>\n<p>Interestingly, PLD3 mutations that cause spinocerebellar ataxia 46, a rare neurodegenerative disease, or that increase Alzheimer\u2019s risk also reduce BMP synthesis. Similar results on brain lipids were found when PLD3 was knocked out in mice.<\/p>\n<p>\u201cThe paper\u2019s findings that these two related enzymes, PLD3 and PLD4, produce BMP fills in a significant piece in the BMP puzzle, and these enzymes do so in an elegant way that results in inversion of the stereochemistry, or handedness, of parts of the molecule,\u201d says Jeremy Baskin, a cell biologist at Cornell University, who was not involved in the work.<\/p>\n<p>Baskin adds that the study expands the field\u2019s understanding of PLD3 and PLD4, because unlike other members of the phospholipase D class, the functions of these two enzymes were not well understood.<\/p>\n<p>In fact, he says that PLD3 and PLD4 were once thought to only break down nucleic acids, but now they appear to have a new role in making a lipid. Walther says that was just one of the surprising results.<\/p>\n<p>\u201cWe were also surprised because other people had reported that another enzyme could make BMP,\u201d he says. That enzyme could make BMP, but it was the wrong stereochemical form.<\/p>\n<p>Now that the team knows more about a crucial step in BMP synthesis, they are looking at the lipid\u2019s role in other\u00a0neurodegenerative diseases. And although they haven\u2019t considered therapies based on their findings yet, it is possible that such approaches could help patients in the future.<\/p>\n<p>In the end, Walther explains, the work is a demonstration of the value of basic research.<\/p>\n<p>\u201cIt really took us sitting down and drawing out the pathways with persistence and a little bit of serendipity to go after this,\u201d he says.<\/p>\n<p>\u201cThere are so many of these unturned stones and fundamental discoveries left to be made.\u201d<\/p>\n<h2 class=\"wp-block-heading\">About this dementia and neurology research news<\/h2>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author:<\/strong><a href=\"http:\/\/www.hhmi.org\/index.html\" target=\"_blank\" rel=\"noreferrer noopener\"><strong> <\/strong>Tobias Walther<\/a><br \/><strong>Source: <\/strong><a href=\"http:\/\/www.hhmi.org\/index.html\" target=\"_blank\" rel=\"noreferrer noopener\">HHMI<\/a><br \/><strong>Contact: <\/strong>Tobias Walther \u2013 HHMI<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:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(24)01094-8\" target=\"_blank\" rel=\"noreferrer noopener\">PLD3 and PLD4 synthesize S,S-BMP, a key phospholipid enabling lipid degradation in lysosomes<\/a>\u201d by Tobias Walther et al. <em>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>PLD3 and PLD4 synthesize S,S-BMP, a key phospholipid enabling lipid degradation in lysosomes<\/strong><\/p>\n<p>Bis(monoacylglycero)phosphate (BMP) is an abundant lysosomal phospholipid required for degradation of lipids, particularly gangliosides. Alterations in BMP levels are associated with neurodegenerative diseases.<\/p>\n<p>Unlike typical glycerophospholipids, lysosomal BMP has two chiral glycerol carbons in the\u00a0<em>S<\/em>\u00a0(rather than the\u00a0<em>R<\/em>) stereo-conformation, protecting it from lysosomal degradation. How this unusual and yet crucial\u00a0<em>S<\/em>,<em>S-<\/em>stereochemistry is achieved is unknown.<\/p>\n<p>Here, we report that phospholipases D3 and D4 (PLD3 and PLD4) synthesize lysosomal\u00a0<em>S<\/em>,<em>S-<\/em>BMP, with either enzyme catalyzing the critical glycerol stereo-inversion reaction\u00a0<em>in\u00a0vitro<\/em>.<\/p>\n<p>Deletion of PLD3 or PLD4 markedly reduced BMP levels in cells or in murine tissues where either enzyme is highly expressed (brain for PLD3; spleen for PLD4), leading to gangliosidosis and lysosomal abnormalities.<\/p>\n<p>PLD3 mutants associated with neurodegenerative diseases, including risk of Alzheimer\u2019s disease, diminished PLD3 catalytic activity.<\/p>\n<p>We conclude that PLD3\/4 enzymes synthesize lysosomal\u00a0<em>S<\/em>,<em>S-<\/em>BMP, a crucial lipid for maintaining brain health.<\/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\/bmp-lipid-dementia-27890\/\">Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Summary: Researchers have discovered how a lipid molecule, BMP, crucial for brain function, is produced, potentially opening new doors for treating neurodegenerative diseases like Alzheimer\u2019s and frontotemporal dementia. Two enzymes, &hellip; <a href=\"https:\/\/hotvideos24.online\/?p=115821\" 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-115821","post","type-post","status-publish","format-standard","hentry","category-health","entry"],"_links":{"self":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/posts\/115821","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=115821"}],"version-history":[{"count":0,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/posts\/115821\/revisions"}],"wp:attachment":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=115821"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=115821"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=115821"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}