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In contrast, neurons can use lactate as an energy substrate: lactate-derived input feeds the mitochondrial tricarboxylic acid cycle and oxidative phosphorylation far more efficiently than glycolysis alone. The hypothesis proposes that glioma-derived lactate preferentially fuels nearby neurons, helping spare glucose for glucose-dependent cancer cells. Glioma-mediated glutamate release may further enhance neuronal lactate uptake, supporting early malignant growth by securing glucose availability before new vasculature develops.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/glioma-neuron-symbiosis-a-hypothesis-hypothesis/370997/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/glioma-neuron-symbiosis-a-hypothesis-hypothesis/370997.png","ImageObject",300,407,{"name":92,"@type":93},"Guten tag","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",17,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What does the hypothesis propose about glioma-derived lactate?","Question",{"text":113,"@type":114},"It proposes that lactate produced by glioma cells is the preferred oxidative energy substrate for surrounding neurons.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How do neurons use lactate differently from glycolysis alone?",{"text":118,"@type":114},"Neurons use lactate to enter mitochondrial metabolism through the tricarboxylic acid cycle and oxidative phosphorylation, which is described as far more efficient at ATP production than glycolysis alone.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is sparing glucose important for the early stages of malignancy in this hypothesis?",{"text":122,"@type":114},"By redirecting neuronal energy use toward lactate, neurons bypass glycolysis and preserve glucose, making it more readily available for glucose-craving cancer cells before additional vasculature develops.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},370997,1790444904,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":46},687212321768,"https://ap-avatar.wpscdn.com/avatar/a0010bdbe886d2fe77?x-image-process=image/resize,m_fixed,w_180,h_180&k=1789897067658708522","TYPE Hypothesis and Theory PUBLISHED 30 September 2025 DOI 10.3389/fnins.2025.1646148  \nOPEN ACCESS  \nEDITED BY  \nFrancesco Bruno,  \nUniversity and City of Health and Science Hospital, Italy  \nREVIEWED BY  \nThomas Daubon,  \nUMR5095 Institut de Biochimie et Génétique Cellulaires (IBGC), France  \nGeorge A. Brooks,  \nUniversity of California, Berkeley, United States  \n*CORRESPONDENCE  \nAvital Schurr  \n [avital.schurr@gmail.com](avital.schurr@gmail.com)  \nRECEIVED 12 June 2025  \nACCEPTED 17 September 2025  \nPUBLISHED 30 September 2025  \nCITATION  \nSchurr A (2025) Glioma neuron symbiosis: a hypothesis.  \nFront. Neurosci. 19:1646148 .  \ndoi: 10.3389/fnins.2025.1646148  \nCOPYRIGHT  \n© 2025 Schurr. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nGlioma neuron symbiosis: a hypothesis  \nAvital Schurr *  \nDepartment of Anesthesiology and Perioperative Medicine, University of Louisville School of Medicine, Louisville, KY, United States  \nGlioma cells, just like all cancerous cells, consume substantial amounts of glucose for their energy needs, using glycolysis, an inefficient metabolic pathway (Warburg effect) to produce only two moles of adenosine triphosphate and two moles of lactate for each mole of glucose consumed. By contrast, neurons consume glucose via glycolysis and utilize its end-product lactate as the substrate of the mitochondrial tricarboxylic acid cycle and its coupled oxidative phosphorylation, a process eighteen times more efficient at adenosine triphosphate than glycolysis alone. It hypothesizes here that glioma-produced lactate is the preferred oxidative energy substrate of their surrounding neurons. Consequently, by using lactate, neurons bypass glycolysis, sparing their glucose and making it readily available for the glucose-craving cancer cells. Moreover, glioma cells’ ability to secrete glutamate, which excites glutamatergic neurons, could drive the latter to consume even more lactate, sparing more glucose. Such symbiotic exchange, especially at the initial stages of malignancy, assures the budding cancer cells an ample glucose supply ahead of the development of additional vasculature. While this hypothesis focuses on gliomas, it may also apply to other cancer types.  \nKEYWORDS  \ncancer, energy metabolism, glioma, glucose, glycolysis, lactate, neuron, symbiosis  \nIntroduction  \nA century ago, Otto Warburg showed that cancer cells consume substantial amounts of glucose and secrete excessive lactate (Warburg et al., 1927) . This hallmark of malignancy, known as Warburg’s effect, was cited over 28,700 times since 1926 and over 5,200 times in the first 6 months of 2025, according to a Google Scholar search. The main impetus for this activity has always been the pursuit of possible anti-cancer therapy through understanding this phenomenon. Nevertheless, Warburg’s observation that cancerous cells utilize glucose glycolytically converting it to lactate, despite the presence of oxygen stood in contrast to the accepted knowledge that respirating cells converting glucose to CO2 and water. The general notion that lactate is a useless end-product of fermentation that also could be, at elevated levels, poisonous to normal cells, has prevailed for years. Our understanding of the relationships between cancer cells and the normal cells that surround them has grown significantly over the past half a century. Most existing research focuses on the interactions between cancerous tissue and neighboring healthy tissue in relation to tumor growth and persistence (Cuddapah et al., 2014; Venkataramani et al., 2022; Crivii et al., 2022; Gillespi","cbCaikul7CZBuXGM","https://ap.wps.com/l/cbCaikul7CZBuXGM","pdf",1018591,"English","# Introduction\n## Warburg’s effect and metabolic context\n## Neuron–cancer metabolic relationships\n# Glycolysis and lactate trafficking\n## Mitochondrial uptake via MCT\n## Lactate conversion to pyruvate and TCA entry","[{\"question\":\"What does the hypothesis propose about glioma-derived lactate?\",\"answer\":\"It proposes that lactate produced by glioma cells is the preferred oxidative energy substrate for surrounding neurons.\"},{\"question\":\"How do neurons use lactate differently from glycolysis alone?\",\"answer\":\"Neurons use lactate to enter mitochondrial metabolism through the tricarboxylic acid cycle and oxidative phosphorylation, which is described as far more efficient at ATP production than glycolysis alone.\"},{\"question\":\"Why is sparing glucose important for the early stages of malignancy in this hypothesis?\",\"answer\":\"By redirecting neuronal energy use toward lactate, neurons bypass glycolysis and preserve glucose, making it more readily available for glucose-craving cancer cells before additional vasculature develops.\"}]","Glioma neuron symbiosis: a hypothesis - Hypothesis | PDF",1790190971]