{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:19:13Z","timestamp":1788153553378,"version":"build-2803163510"},"reference-count":167,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82571627"],"award-info":[{"award-number":["82571627"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82271483"],"award-info":[{"award-number":["82271483"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82571627"],"award-info":[{"award-number":["82571627"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82271483"],"award-info":[{"award-number":["82271483"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Shandong Province Natural Science Foundation of China","award":["ZR2024MH112"],"award-info":[{"award-number":["ZR2024MH112"]}]},{"name":"Shandong Provincial Medical and Health Science and Technology Development Plan","award":["202402010641"],"award-info":[{"award-number":["202402010641"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by the selective degeneration of upper and lower motor neurons (MNs). Although the specific pathogenesis of ALS is not yet fully understood, there is increasing evidence that abnormal energy metabolism plays a key role in the onset and progression of the disease. Lactate has traditionally been considered a metabolic by-product of glycolysis and has received increasing attention in recent years. Research has shown that lactate is not only an important energy substrate but also a signaling molecule that regulates a variety of physiological processes, including neuron-glia metabolic coupling, neuroprotection and inflammatory responses. In ALS, abnormalities in lactate metabolism, dysfunction of the lactate shuttle, and dysregulation of lactate-related signaling pathways may jointly lead to neuronal energy deficits and increased neuroinflammation, thereby promoting MN degeneration. This review summarizes the latest advances in lactate metabolism and lactate-mediated signaling in ALS, with particular emphasis on their roles in neuronal energy regulation, neuroprotection and inflammatory regulation. In addition, we also discuss potential therapeutic strategies for lactate metabolism and its related pathways, aiming to provide new insights into the pathogenesis of ALS and the development of treatment methods for lactate-related metabolism.<\/jats:p>","DOI":"10.3390\/cells15171571","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:08:58Z","timestamp":1788142138000},"page":"1571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactate Metabolism and Signaling in Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Xiaonan","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"},{"name":"Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao 266000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1813-9964","authenticated-orcid":false,"given":"Yingjun","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3856-6145","authenticated-orcid":false,"given":"Chunjie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2719-8657","authenticated-orcid":false,"given":"Mu","family":"Li","sequence":"additional","affiliation":[{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongze","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3527-2191","authenticated-orcid":false,"given":"Xuemei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7777-138X","authenticated-orcid":false,"given":"Yanchun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Goffin, L., Lemoine, D., and Clotman, F. (2024). Potential contribution of spinal interneurons to the etiopathogenesis of amyotrophic lateral sclerosis. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1434404"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gunes, Z.I., Kan, V.W.Y., Ye, X., and Liebscher, S. (2020). Exciting Complexity: The Role of Motor Circuit Elements in ALS Pathophysiology. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00573"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mejzini, R., Flynn, L.L., Pitout, I.L., Fletcher, S., Wilton, S.D., and Akkari, P.A. (2019). ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now? Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01310"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Le Gall, L., Anakor, E., Connolly, O., Vijayakumar, U.G., Duddy, W.J., and Duguez, S. (2020). Molecular and Cellular Mechanisms Affected in ALS. J. Pers. Med., 10.","DOI":"10.1186\/s13395-020-00238-1"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lee, A., Henderson, R., Aylward, J., and McCombe, P. (2024). Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031871"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12950-025-00460-y","article-title":"The metabolic intersection between immunosenescence and neuroinflammation in amyotrophic lateral sclerosis","volume":"22","author":"Tsang","year":"2025","journal-title":"J. Inflamm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1186\/s13023-025-04042-2","article-title":"Concurrent nanotherapeutics and regulatory updates for the management of amyotrophic lateral sclerosis: A focused review for orphan drug (Tofersen)","volume":"20","author":"Kumar","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.tem.2025.02.004","article-title":"Hidden players in the metabolic vulnerabilities of amyotrophic lateral sclerosis","volume":"36","author":"Rosina","year":"2025","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Maksimovic, K., Youssef, M., You, J., Sung, H.-K., and Park, J. (2023). Evidence of Metabolic Dysfunction in Amyotrophic Lateral Sclerosis (ALS) Patients and Animal Models. Biomolecules, 13.","DOI":"10.3390\/biom13050863"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/s41582-023-00845-8","article-title":"Nutritional and metabolic factors in amyotrophic lateral sclerosis","volume":"19","author":"Ludolph","year":"2023","journal-title":"Nat. Rev. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e70080","DOI":"10.1002\/glia.70080","article-title":"C9orf72 Repeat Expansion Induces Metabolic Dysfunction in Human iPSC-Derived Microglia and Modulates Glial-Neuronal Crosstalk","volume":"74","author":"Mearelli","year":"2026","journal-title":"Glia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/ana.25661","article-title":"Effect of High-Caloric Nutrition on Survival in Amyotrophic Lateral Sclerosis","volume":"87","author":"Ludolph","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Frazier, H.N., Ghoweri, A.O., Anderson, K.L., Lin, R.-L., Popa, G.J., Mendenhall, M.D., Reagan, L.P., Craven, R.J., and Thibault, O. (2020). Elevating Insulin Signaling Using a Constitutively Active Insulin Receptor Increases Glucose Metabolism and Expression of GLUT3 in Hippocampal Neurons. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00668"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nrn.2018.19","article-title":"Lactate in the brain: From metabolic end-product to signalling molecule","volume":"19","author":"Magistretti","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s12974-024-03303-4","article-title":"Lactate metabolism and histone lactylation in the central nervous system disorders: Impacts and molecular mechanisms","volume":"21","author":"Wang","year":"2024","journal-title":"J. Neuroinflammation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4196\/kjpp.24.388","article-title":"Brain energy homeostasis: The evolution of the astrocyte-neuron lactate shuttle hypothesis","volume":"29","author":"Kim","year":"2025","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s12964-025-02132-z","article-title":"L- and D-Lactate: Unveiling their hidden functions in disease and health","volume":"23","author":"Li","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/s42255-020-0243-4","article-title":"Lactate: The ugly duckling of energy metabolism","volume":"2","author":"Rabinowitz","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1056\/NEJMra1309483","article-title":"Lactic acidosis","volume":"371","author":"Kraut","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1080\/146608202760196011","article-title":"Impaired oxidative metabolism and lipid peroxidation in exercising muscle from ALS patients","volume":"3","author":"Siciliano","year":"2002","journal-title":"Amyotroph. Lateral Scler. Other Mot. Neuron Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s40170-025-00392-4","article-title":"Lactate dehydrogenase A-coupled NAD+ regeneration is critical for acute myeloid leukemia cell survival","volume":"13","author":"Erdem","year":"2025","journal-title":"Cancer Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.molcel.2020.12.012","article-title":"Increased demand for NAD+ relative to ATP drives aerobic glycolysis","volume":"81","author":"Luengo","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/s41586-019-1678-1","article-title":"Metabolic regulation of gene expression by histone lactylation","volume":"574","author":"Zhang","year":"2019","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chen, A.N., Luo, Y., Yang, Y.-H., Fu, J.-T., Geng, X.-M., Shi, J.-P., and Yang, J. (2021). Lactylation, a Novel Metabolic Reprogramming Code: Current Status and Prospects. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.688910"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, Y.M., Yang, F., Li, Q., and Zhang, J.-N. (2025). Role of Histone Lactylation in Neurological Disorders. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26167949"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6842","DOI":"10.1038\/s41467-024-51008-2","article-title":"A lactate-dependent shift of glycolysis mediates synaptic and cognitive processes in male mice","volume":"15","author":"Lavanco","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3934\/Neuroscience.2020007","article-title":"Astrocytes and neurons communicate via a monocarboxylic acid shuttle","volume":"7","author":"Roosterman","year":"2020","journal-title":"AIMS Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5979","DOI":"10.1038\/s41467-024-50166-7","article-title":"Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture","volume":"15","author":"Braga","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1111\/joor.13847","article-title":"The Role of Astrocyte-Neuron Lactate Shuttle in Neuropathic Orofacial Pain","volume":"51","author":"Hu","year":"2024","journal-title":"J. Oral Rehabil."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wu, A., Lee, D., and Xiong, W.C. (2023). Lactate Metabolism, Signaling, and Function in Brain Development, Synaptic Plasticity, Angiogenesis, and Neurodegenerative Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713398"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e202302535","DOI":"10.26508\/lsa.202302535","article-title":"Glycolic acid and D-lactate-putative products of DJ-1-restore neurodegeneration in FUS\u2014And SOD1-ALS","volume":"7","author":"Pal","year":"2024","journal-title":"Life Sci. Alliance"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2025.06.012","article-title":"PKM2 alleviates mitochondrial oxidative stress and neuronal apoptosis through metabolic and non-metabolic pathways to protect SOD1(G93A) mice","volume":"238","author":"Zhang","year":"2025","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/bs.irn.2026.05.012","article-title":"Energetic crisis, mitochondrial vulnerability and disruption of lactate shuttle in Alzheimer\u2019s disease","volume":"188","author":"Baskar","year":"2026","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s10020-026-01551-z","article-title":"Lactate dynamics in Parkinson\u2019s disease: Striatal circuit vulnerability, biomarker potential, and therapeutic windows","volume":"32","author":"Kong","year":"2026","journal-title":"Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102452","DOI":"10.1016\/j.arr.2024.102452","article-title":"Friend or foe: Lactate in neurodegenerative diseases","volume":"101","author":"Wang","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.cmet.2018.03.008","article-title":"The Science and Translation of Lactate Shuttle Theory","volume":"27","author":"Brooks","year":"2018","journal-title":"Cell Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e2212004119","DOI":"10.1073\/pnas.2212004119","article-title":"Lactate supply overtakes glucose when neural computational and cognitive loads scale up","volume":"119","author":"Dembitskaya","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1113\/jphysiol.2003.058701","article-title":"Lactate metabolism: A new paradigm for the third millennium","volume":"558","author":"Gladden","year":"2004","journal-title":"J. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.mayocp.2013.06.012","article-title":"Etiology and therapeutic approach to elevated lactate levels","volume":"88","author":"Andersen","year":"2013","journal-title":"Mayo Clin. Proc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg Effect: How Does it Benefit Cancer Cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nature24057","article-title":"Glucose feeds the TCA cycle via circulating lactate","volume":"551","author":"Hui","year":"2017","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101454","DOI":"10.1016\/j.redox.2020.101454","article-title":"Lactate as a fulcrum of metabolism","volume":"35","author":"Brooks","year":"2020","journal-title":"Redox Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/cc1518","article-title":"Bench-to-bedside review: Lactate and the kidney","volume":"6","author":"Bellomo","year":"2002","journal-title":"Crit. Care"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1464-5491.2009.02894.x","article-title":"Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: Therapeutic implications","volume":"27","author":"Gerich","year":"2010","journal-title":"Diabet. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E126","DOI":"10.1152\/ajpendo.00306.2024","article-title":"The mitochondrial lactate oxidation complex: Endpoint for carbohydrate carbon disposal","volume":"328","author":"Leija","year":"2025","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.nbt.2012.05.021","article-title":"Lactate metabolism shift in CHO cell culture: The role of mitochondrial oxidative activity","volume":"30","author":"Zagari","year":"2013","journal-title":"New Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1113\/jphysiol.2003.055053","article-title":"A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain","volume":"554","author":"Dalsgaard","year":"2004","journal-title":"J. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bartoloni, B., Mannelli, M., Gamberi, T., and Fiaschi, T. (2024). The Multiple Roles of Lactate in the Skeletal Muscle. Cells, 13.","DOI":"10.3390\/cells13141177"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.cell.2011.02.018","article-title":"Astrocyte-neuron lactate transport is required for long-term memory formation","volume":"144","author":"Suzuki","year":"2011","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/s12276-022-00802-3","article-title":"Tracing the lactate shuttle to the mitochondrial reticulum","volume":"54","author":"Brooks","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.molmet.2019.07.006","article-title":"Monocarboxylate transporters in cancer","volume":"33","author":"Payen","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/iub.572","article-title":"The monocarboxylate transporter family\u2014Role and regulation","volume":"64","author":"Halestrap","year":"2012","journal-title":"IUBMB Life"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"eadn4508","DOI":"10.1126\/sciadv.adn4508","article-title":"Lactate transported by MCT1 plays an active role in promoting mitochondrial biogenesis and enhancing TCA flux in skeletal muscle","volume":"10","author":"Zhang","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"load041","DOI":"10.1093\/lifemeta\/load041","article-title":"Intestinal monocarboxylate transporter 1 mediates lactate transport in the gut and regulates metabolic homeostasis of mouse in a sex-dimorphic pattern","volume":"3","author":"Wang","year":"2024","journal-title":"Life Metab."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Maculewicz, E., Mastalerz, A., Garbacz, A., Mr\u00f3z, A., Stastny, P., Petr, M., Kolinger, D., Vostatkov\u00e1, P., and Bojarczuk, A. (2025). The interactions between monocarboxylate transporter genes MCT1, MCT2, and MCT4 and the kinetics of blood lactate production and removal after high-intensity efforts in elite males: A cross-sectional study. BMC Genom., 26.","DOI":"10.1186\/s12864-025-11307-4"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Seki, S., Kobayashi, T., Kikuchi, N., Hoshina, K., and Hwang, I. (2025). Muscle Oxygen Saturation Responses During Maximal and Submaximal Exercise According to SLC16A1 (MCT1) Gene Polymorphism in Long-Distance Runners: A Cross-Sectional Pilot Study. Genes, 16.","DOI":"10.3390\/genes16111324"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"176510","DOI":"10.1016\/j.ejphar.2024.176510","article-title":"Role of monocarboxylate transporters in AMPK-mediated protection against excitotoxic injury in the rat retina","volume":"970","author":"Yamagishi","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1006\/bbrc.1997.6588","article-title":"Identification of a unique monocarboxylate transporter (MCT3) in retinal pigment epithelium","volume":"234","author":"Yoon","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"C451","DOI":"10.1152\/ajpcell.00124.2008","article-title":"Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice","volume":"295","author":"Daniele","year":"2008","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1186\/s12964-025-02326-5","article-title":"Strengthening monocarboxylate transporters by adiponectin receptor agonist ameliorates diabetic peripheral neuropathy","volume":"23","author":"Kim","year":"2025","journal-title":"Cell Commun. Signal"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s13018-023-03623-w","article-title":"Functional heterogeneity of MCT1 and MCT4 in metabolic reprogramming affects osteosarcoma growth and metastasis","volume":"18","author":"Sheng","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"jcs261608","DOI":"10.1242\/jcs.261608","article-title":"MCT4 and CD147 colocalize with MMP14 in invadopodia and support matrix degradation and invasion by breast cancer cells","volume":"137","author":"Meng","year":"2024","journal-title":"J. Cell Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"216824","DOI":"10.1016\/j.canlet.2024.216824","article-title":"Targeting tumor-intrinsic SLC16A3 to enhance anti-PD-1 efficacy via tumor immune microenvironment reprogramming","volume":"589","author":"Yu","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/s41392-022-01151-3","article-title":"Lactate metabolism in human health and disease","volume":"7","author":"Li","year":"2022","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.cmet.2010.02.012","article-title":"An autocrine lactate loop mediates insulin-dependent inhibition of lipolysis through GPR81","volume":"11","author":"Ahmed","year":"2010","journal-title":"Cell Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1074\/jbc.M806409200","article-title":"Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81","volume":"284","author":"Liu","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.cmet.2024.12.009","article-title":"Lactate homeostasis is maintained through regulation of glycolysis and lipolysis","volume":"37","author":"Lee","year":"2025","journal-title":"Cell Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"15557","DOI":"10.1038\/ncomms15557","article-title":"Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1","volume":"8","author":"Morland","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"12228","DOI":"10.1073\/pnas.1322912111","article-title":"Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons","volume":"111","author":"Yang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s12964-023-01188-z","article-title":"Lack of HCAR1, the lactate GPCR, signaling promotes autistic-like behavior","volume":"21","author":"Nezhady","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"109679","DOI":"10.1016\/j.isci.2024.109679","article-title":"The lactate receptor HCAR1: A key modulator of epileptic seizure activity","volume":"27","author":"Alessandri","year":"2024","journal-title":"iScience"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"ENEURO-0563","DOI":"10.1523\/ENEURO.0563-24.2025","article-title":"Lactate Receptor HCAR1 Affects Axonal Development and Contributes to Lactate\u2019s Protection of Axons and Myelin in Experimental Neonatal Hypoglycemia","volume":"12","author":"Kennedy","year":"2025","journal-title":"eNeuro"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1053\/j.gastro.2014.03.014","article-title":"Lactate reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated suppression of innate immunity","volume":"146","author":"Hoque","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Li, X., Yao, Z., Qian, J., Li, H., and Li, H. (2024). Lactate Protects Intestinal Epithelial Barrier Function from Dextran Sulfate Sodium-Induced Damage by GPR81 Signaling. Nutrients, 16.","DOI":"10.3390\/nu16050582"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1158\/0008-5472.CAN-14-0319","article-title":"Cell surface lactate receptor GPR81 is crucial for cancer cell survival","volume":"74","author":"Roland","year":"2014","journal-title":"Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1097\/HEP.0000000000000569","article-title":"Canonical Wnt signaling promotes HSC glycolysis and liver fibrosis through an LDH-A\/HIF-1\u03b1 transcriptional complex","volume":"79","author":"Wang","year":"2024","journal-title":"Hepatology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1093\/neuonc\/noae040","article-title":"HIF1\u03b1\/ATF3 partake in PGK1 K191\/K192 succinylation by modulating P4HA1\/succinate signaling in glioblastoma","volume":"26","author":"Yang","year":"2024","journal-title":"Neuro Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/s41418-024-01436-w","article-title":"ABCF1-K430-Lactylation promotes HCC malignant progression via transcriptional activation of HIF1 signaling pathway","volume":"32","author":"Hong","year":"2025","journal-title":"Cell Death Differ."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"114180","DOI":"10.1016\/j.celrep.2024.114180","article-title":"Macrophage MCT4 inhibition activates reparative genes and protects from atherosclerosis by histone H3 lysine 18 lactylation","volume":"43","author":"Zhang","year":"2024","journal-title":"Cell Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12933-024-02178-2","article-title":"MCT4-dependent lactate transport: A novel mechanism for cardiac energy metabolism injury and inflammation in type 2 diabetes mellitus","volume":"23","author":"Ma","year":"2024","journal-title":"Cardiovasc Diabetol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e187849","DOI":"10.1172\/jci.insight.187849","article-title":"Enhancing mitochondrial pyruvate metabolism ameliorates ischemic reperfusion injury in the heart","volume":"9","author":"Visker","year":"2024","journal-title":"JCI Insight"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/jcbfm.2015.77","article-title":"Is L-lactate a novel signaling molecule in the brain?","volume":"35","author":"Mosienko","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1073\/pnas.1614035114","article-title":"Gpr132 sensing of lactate mediates tumor-macrophage interplay to promote breast cancer metastasis","volume":"114","author":"Chen","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s13258-025-01622-1","article-title":"Lactate released by lung adenocarcinoma (LUAD) cells promotes M2 macrophage polarization via the GPR132\/cAMP\/PKA pathway","volume":"47","author":"Chen","year":"2025","journal-title":"Genes Genom."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1038\/s41467-024-47900-6","article-title":"HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription","volume":"15","author":"Niu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s43556-025-00275-6","article-title":"Histone and non-histone lactylation: Molecular mechanisms, biological functions, diseases, and therapeutic targets","volume":"6","author":"Peng","year":"2025","journal-title":"Mol. BioMed."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1093\/cercor\/bht136","article-title":"Lactate receptor sites link neurotransmission, neurovascular coupling, and brain energy metabolism","volume":"24","author":"Lauritzen","year":"2014","journal-title":"Cereb. Cortex"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Chen, L., Huang, L., Gu, Y., Cang, W., Sun, P., and Xiang, Y. (2022). Lactate-Lactylation Hands between Metabolic Reprogramming and Immunosuppression. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911943"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.chembiol.2019.11.005","article-title":"Non-enzymatic Lysine Lactoylation of Glycolytic Enzymes","volume":"27","author":"Gaffney","year":"2020","journal-title":"Cell Chem. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"101923","DOI":"10.1016\/j.molmet.2024.101923","article-title":"Histone lactylation in macrophages is predictive for gene expression changes during ischemia induced-muscle regeneration","volume":"83","author":"Desgeorges","year":"2024","journal-title":"Mol. Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1515\/mr-2024-0091","article-title":"Histone lactylation as a driver of metabolic reprogramming and immune evasion","volume":"5","author":"Cai","year":"2024","journal-title":"Med. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41420-025-02748-7","article-title":"Histone lactylation-induced GLI3 activation drives macrophage M1 polarization and exosomal SERPINE1 release in abdominal aortic aneurysm progression","volume":"11","author":"Yuan","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.immuni.2024.04.006","article-title":"Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma","volume":"57","author":"Ugolini","year":"2024","journal-title":"Immunity"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41531-024-00858-0","article-title":"Enhanced glycolysis-derived lactate promotes microglial activation in Parkinson\u2019s disease via histone lactylation","volume":"11","author":"Qin","year":"2025","journal-title":"npj Park. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"109820","DOI":"10.1016\/j.celrep.2021.109820","article-title":"Protein lactylation induced by neural excitation","volume":"37","author":"Hagihara","year":"2021","journal-title":"Cell Rep."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Chen, Y., Xiao, D., and Li, X. (2025). Lactylation and Central Nervous System Diseases. Brain Sci., 15.","DOI":"10.3390\/brainsci15030294"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e188077","DOI":"10.1172\/jci.insight.188077","article-title":"H3K18 lactylation potentiates microglial polarization via the TLR4 pathway in diabetes-induced cognitive impairment","volume":"10","author":"Yang","year":"2025","journal-title":"JCI Insight"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41419-025-07498-z","article-title":"Histone lactylation enhances GCLC expression and thus promotes chemoresistance of colorectal cancer stem cells through inhibiting ferroptosis","volume":"16","author":"Deng","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1016\/j.apsb.2024.03.008","article-title":"ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT","volume":"14","author":"Dong","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41392-024-02082-x","article-title":"Lactate and lactylation in cancer","volume":"10","author":"Chen","year":"2025","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1284344","DOI":"10.3389\/fimmu.2023.1284344","article-title":"Histone lactylation regulates cancer progression by reshaping the tumor microenvironment","volume":"14","author":"Qu","year":"2023","journal-title":"Front Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Tendulkar, S., Wu, T., Strickland, A., Hackett, A.R., Sato-Yamada, Y., Mao, X., Sasaki, Y., Milbrandt, J., Bloom, A.J., and DiAntonio, A. (2026). Dysregulated lactate metabolism synergizes with ALS genetic risk factors to accelerate motor decline. PLoS ONE, 21.","DOI":"10.1371\/journal.pone.0347135"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/glia.23114","article-title":"Wildtype motoneurons, ALS-Linked SOD1 mutation and glutamate profoundly modify astrocyte metabolism and lactate shuttling","volume":"65","author":"Hounoum","year":"2017","journal-title":"Glia"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1002\/ana.78184","article-title":"Blood Lactate as a Prognostic Biomarker for Survival and Weight Loss in Amyotrophic Lateral Sclerosis: An Exploratory-Validation Study","volume":"99","author":"Nakamura","year":"2026","journal-title":"Ann. Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e45114","DOI":"10.7554\/eLife.45114","article-title":"Glycolysis upregulation is neuroprotective as a compensatory mechanism in ALS","volume":"8","author":"Manzo","year":"2019","journal-title":"eLife"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/jnc.14819","article-title":"Altered glucose catabolism in the presynaptic and perisynaptic compartments of SOD1(G93A) mouse spinal cord and motor cortex indicates that mitochondria are the site of bioenergetic imbalance in ALS","volume":"151","author":"Ravera","year":"2019","journal-title":"J. Neurochem"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1177\/0271678X18756499","article-title":"Evolution of the neurochemical profiles in the G93A-SOD1 mouse model of amyotrophic lateral sclerosis","volume":"39","author":"Lei","year":"2019","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3109\/21678421.2015.1053490","article-title":"The longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis","volume":"16","author":"Gray","year":"2015","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"20786","DOI":"10.1038\/s41598-021-00312-8","article-title":"Characteristics of serum metabolites in sporadic amyotrophic lateral sclerosis patients based on gas chromatography-mass spectrometry","volume":"11","author":"Jia","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s40478-020-01018-0","article-title":"Defining novel functions for cerebrospinal fluid in ALS pathophysiology","volume":"8","author":"Kwong","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Alhathli, E., Cooper-Knock, J., Girach, Z.-U., Julian, T.H., Bauer, C., Timmons, H.O., Ward, B.D., Walker, H., Azzouz, M., and Elrayess, M.A. (2026). Hypothesis-free evaluation of circulating metabolome provides cell-specific insights regarding the role of energy substrate availability in amyotrophic lateral sclerosis. BMC Med., 24.","DOI":"10.1186\/s12916-026-04727-w"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Blasco, H., Corcia, P., Moreau, C., Veau, S., Fournier, C., Vourc\u2019H, P., Emond, P., Gordon, P., Pradat, P.-F., and Praline, J. (2010). 1H-NMR-based metabolomic profiling of CSF in early amyotrophic lateral sclerosis. PLoS ONE, 5.","DOI":"10.1371\/annotation\/2c2f8fce-a5be-40a3-af8f-48f119b2c593"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Baker, D.J., Blackburn, D.J., Keatinge, M., Sokhi, D., Viskaitis, P., Heath, P.R., Ferraiuolo, L., Kirby, J., and Shaw, P.J. (2015). Lysosomal and phagocytic activity is increased in astrocytes during disease progression in the SOD1 (G93A) mouse model of amyotrophic lateral sclerosis. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00410"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Valbuena, G.N., Cantoni, L., Tortarolo, M., Bendotti, C., and Keun, H.C. (2019). Spinal Cord Metabolic Signatures in Models of Fast- and Slow-Progressing SOD1(G93A) Amyotrophic Lateral Sclerosis. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01276"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature11314","article-title":"Oligodendroglia metabolically support axons and contribute to neurodegeneration","volume":"487","author":"Lee","year":"2012","journal-title":"Nature"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4103\/0366-6999.172561","article-title":"Elimination Rate of Serum Lactate is Correlated with Amyotrophic Lateral Sclerosis Progression","volume":"129","author":"Zhang","year":"2016","journal-title":"Chin. Med. J."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Cieminski, K., Flis, D.J., Dzik, K.P., Kaczor, J.J., Wieckowski, M.R., Antosiewicz, J., and Ziolkowski, W. (2022). Swim Training Affects on Muscle Lactate Metabolism, Nicotinamide Adenine Dinucleotides Concentration, and the Activity of NADH Shuttle Enzymes in a Mouse Model of Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911504"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/s41418-020-00664-0","article-title":"ALS motor neurons exhibit hallmark metabolic defects that are rescued by SIRT3 activation","volume":"28","author":"Hor","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1038\/s41467-025-59679-1","article-title":"Single-cell RNA-sequencing reveals early mitochondrial dysfunction unique to motor neurons shared across FUS- and TARDBP-ALS","volume":"16","author":"Schweingruber","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1093\/brain\/awr193","article-title":"Dysregulation of astrocyte-motoneuron cross-talk in mutant superoxide dismutase 1-related amyotrophic lateral sclerosis","volume":"134","author":"Ferraiuolo","year":"2011","journal-title":"Brain"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"6003","DOI":"10.1038\/s41598-020-62864-5","article-title":"Astrocytes with TDP-43 inclusions exhibit reduced noradrenergic cAMP and Ca2+ signaling and dysregulated cell metabolism","volume":"10","author":"Velebit","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1093\/brain\/aws339","article-title":"Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis","volume":"136","author":"Philips","year":"2013","journal-title":"Brain"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"E6496","DOI":"10.1073\/pnas.1607496113","article-title":"Oligodendrocytes contribute to motor neuron death in ALS via SOD1-dependent mechanism","volume":"113","author":"Ferraiuolo","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Mouhi, S., Pio, T., and Andersen, J. (2025). Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models. Trends Cell Biol.","DOI":"10.1016\/j.tcb.2025.11.003"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/glia.23889","article-title":"Disrupted function of lactate transporter MCT1, but not MCT4, in Schwann cells affects the maintenance of motor end-plate innervation","volume":"69","author":"Pollmeier","year":"2021","journal-title":"Glia"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"589582","DOI":"10.3389\/fncel.2020.589582","article-title":"Lactate Transporters Mediate Glia-Neuron Metabolic Crosstalk in Homeostasis and Disease","volume":"14","author":"Jha","year":"2020","journal-title":"Front Cell. Neurosci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.brainres.2012.07.040","article-title":"Impaired response of hypoxic sensor protein HIF-1\u03b1 and its downstream proteins in the spinal motor neurons of ALS model mice","volume":"1473","author":"Sato","year":"2012","journal-title":"Brain Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.neuroscience.2010.10.040","article-title":"Deregulation of the hypoxia inducible factor-1\u03b1 pathway in monocytes from sporadic amyotrophic lateral sclerosis patients","volume":"172","author":"Moreau","year":"2011","journal-title":"Neuroscience"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.neuroscience.2019.06.025","article-title":"Imaging Hypoxic Stress and the Treatment of Amyotrophic Lateral Sclerosis with Dimethyloxalylglycine in a Mice Model","volume":"415","author":"Nomura","year":"2019","journal-title":"Neuroscience"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/bpa.12040","article-title":"Impaired cytoplasmic-nuclear transport of hypoxia-inducible factor-1\u03b1 in amyotrophic lateral sclerosis","volume":"23","author":"Nagara","year":"2013","journal-title":"Brain Pathol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"zqae005","DOI":"10.1093\/function\/zqae005","article-title":"Pro-Brain-Derived Neurotrophic Factor (BDNF), but Not Mature BDNF, Is Expressed in Human Skeletal Muscle: Implications for Exercise-Induced Neuroplasticity","volume":"5","author":"Edman","year":"2024","journal-title":"Function"},{"key":"ref_132","first-page":"2369","article-title":"Lactate Mediates the Effects of Exercise on Learning and Memory through SIRT1-Dependent Activation of Hippocampal Brain-Derived Neurotrophic Factor (BDNF)","volume":"39","author":"Khalifeh","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Arnold, F.J., Putka, A.F., Raychaudhuri, U., Hsu, S., Bedlack, R.S., Bennett, C.L., and La Spada, A.R. (2024). Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115587"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.bbadis.2012.11.013","article-title":"Role of the N-methyl-d-aspartate receptors complex in amyotrophic lateral sclerosis","volume":"1832","author":"Spalloni","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Riolo, G., Ricci, C., De Angelis, N., Marzocchi, C., Guerrera, G., Borsellino, G., Giannini, F., and Battistini, S. (2022). BDNF and Pro-BDNF in Amyotrophic Lateral Sclerosis: A New Perspective for Biomarkers of Neurodegeneration. Brain Sci., 12.","DOI":"10.3390\/brainsci12050617"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1097\/00001756-199805110-00073","article-title":"Neutrophin switching in spinal motoneurons of amyotrophic lateral sclerosis","volume":"9","author":"Nishio","year":"1998","journal-title":"NeuroReport"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1097\/00005072-199809000-00003","article-title":"Immunohistochemical localization of brain-derived neurotrophic factor in the spinal cords of amyotrophic lateral sclerosis and non-amyotrophic lateral sclerosis patients","volume":"57","author":"Kawamoto","year":"1998","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.cmet.2012.03.019","article-title":"Elevated PGC-1\u03b1 activity sustains mitochondrial biogenesis and muscle function without extending survival in a mouse model of inherited ALS","volume":"15","author":"Parone","year":"2012","journal-title":"Cell Metab."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.nbd.2016.11.001","article-title":"ALS-causing mutations differentially affect PGC-1\u03b1 expression and function in the brain vs. peripheral tissues","volume":"97","author":"Bayer","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1097\/NEN.0b013e318275df4b","article-title":"Decreased mRNA expression of PGC-1\u03b1 and PGC-1\u03b1-regulated factors in the SOD1G93A ALS mouse model and in human sporadic ALS","volume":"71","author":"Thau","year":"2012","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/mus.22217","article-title":"PGC-1\u03b1 protects neurons and alters disease progression in an amyotrophic lateral sclerosis mouse model","volume":"44","author":"Liang","year":"2011","journal-title":"Muscle Nerve"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/WCO.0000000000001162","article-title":"Cortical hyperexcitability in amyotrophic lateral sclerosis: From pathogenesis to diagnosis","volume":"36","author":"Timmins","year":"2023","journal-title":"Curr. Opin. Neurol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"136039","DOI":"10.1016\/j.neulet.2021.136039","article-title":"Cortical hyperexcitability: Diagnostic and pathogenic biomarker of ALS","volume":"759","author":"Vucic","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1089\/ars.2009.2444","article-title":"Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis","volume":"11","author":"Foran","year":"2009","journal-title":"Antioxid. Redox Signal"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Stacchiotti, C., di Regnella, S.M., Cinotti, M., Spalloni, A., and Volpe, E. (2025). Neuroinflammation and Amyotrophic Lateral Sclerosis: Recent Advances in Anti-Inflammatory Cytokines as Therapeutic Strategies. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083854"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4103\/1673-5374.374142","article-title":"Lactate metabolism in neurodegenerative diseases","volume":"19","author":"Yang","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1159\/000089626","article-title":"Hypermetabolism in ALS: Correlations with clinical and paraclinical parameters","volume":"2","author":"Desport","year":"2005","journal-title":"Neurodegener. Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1007\/s00415-009-5100-z","article-title":"Hypermetabolism in ALS patients: An early and persistent phenomenon","volume":"256","author":"Bouteloup","year":"2009","journal-title":"J. Neurol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1136\/jnnp-2017-317887","article-title":"Hypermetabolism in ALS is associated with greater functional decline and shorter survival","volume":"89","author":"Steyn","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00401-018-1835-x","article-title":"Energy metabolism in ALS: An underappreciated opportunity?","volume":"135","author":"Vandoorne","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3109\/21678421.2013.823999","article-title":"High-caloric food supplements in the treatment of amyotrophic lateral sclerosis: A prospective interventional study","volume":"14","author":"Dorst","year":"2013","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Miquel, E., Cassina, A., Martinez-Palma, L., Bolatto, C., Trias, E., Gandelman, M., Radi, R., Barbeito, L., and Cassina, P. (2012). Modulation of astrocytic mitochondrial function by dichloroacetate improves survival and motor performance in inherited amyotrophic lateral sclerosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034776"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s13311-018-0659-7","article-title":"Mitochondrial Modulation by Dichloroacetate Reduces Toxicity of Aberrant Glial Cells and Gliosis in the SOD1G93A Rat Model of Amyotrophic Lateral Sclerosis","volume":"16","author":"Miquel","year":"2019","journal-title":"Neurotherapeutics"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13041-025-01248-0","article-title":"Integrated molecular data analysis confirms PDK1 as a candidate risk factor in ALS pathophysiology","volume":"18","author":"Liu","year":"2025","journal-title":"Mol. Brain"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1177\/0883073813488669","article-title":"High-fat and ketogenic diets in amyotrophic lateral sclerosis","volume":"28","author":"Paganoni","year":"2013","journal-title":"J. Child Neurol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Tefera, T.W., Wong, Y., E Barkl-Luke, M., Ngo, S.T., Thomas, N.K., McDonald, T.S., and Borges, K. (2016). Triheptanoin Protects Motor Neurons and Delays the Onset of Motor Symptoms in a Mouse Model of Amyotrophic Lateral Sclerosis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161816"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.4103\/NRR.NRR-D-23-01763","article-title":"Bone marrow-derived microglia confer neuroprotection to a mouse model of amyotrophic lateral sclerosis","volume":"19","author":"Solomon","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.omtm.2021.01.006","article-title":"AAV9-mediated gene delivery of MCT1 to oligodendrocytes does not provide a therapeutic benefit in a mouse model of ALS","volume":"20","author":"Eykens","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Jamet, M., Dupuis, L., and De Aguilar, J.-L.G. (2024). Oligodendrocytes in amyotrophic lateral sclerosis and frontotemporal dementia: The new players on stage. Front. Mol. Neurosci., 17.","DOI":"10.3389\/fnmol.2024.1375330"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"5252","DOI":"10.1038\/s41598-019-41771-4","article-title":"Single injection of sustained-release prostacyclin analog ONO-1301-MS ameliorates hypoxic toxicity in the murine model of amyotrophic lateral sclerosis","volume":"9","author":"Tada","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.neulet.2014.02.058","article-title":"7,8-Dihydroxyflavone improves motor performance and enhances lower motor neuronal survival in a mouse model of amyotrophic lateral sclerosis","volume":"566","author":"Korkmaz","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"4422","DOI":"10.1523\/JNEUROSCI.2092-18.2019","article-title":"The Lactate Receptor HCAR1 Modulates Neuronal Network Activity through the Activation of G(\u03b1) and G(\u03b2\u03b3) Subunits","volume":"39","author":"Abrantes","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s41420-025-02408-w","article-title":"The role of protein lactylation in brain health and disease: Current advances and future directions","volume":"11","author":"Han","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1096\/fj.09-130047","article-title":"Neuroprotective and neuritogenic activities of novel multimodal iron-chelating drugs in motor-neuron-like NSC-34 cells and transgenic mouse model of amyotrophic lateral sclerosis","volume":"23","author":"Kupershmidt","year":"2009","journal-title":"Faseb J."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1750-1172-6-10","article-title":"Lack of a synergistic effect of a non-viral ALS gene therapy based on BDNF and a TTC fusion molecule","volume":"6","author":"Calvo","year":"2011","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Yanpallewar, S.U., Barrick, C.A., Buckley, H., Becker, J., and Tessarollo, L. (2012). Deletion of the BDNF truncated receptor TrkB.T1 delays disease onset in a mouse model of amyotrophic lateral sclerosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039946"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1007\/s00018-019-03337-5","article-title":"Running and swimming prevent the deregulation of the BDNF\/TrkB neurotrophic signalling at the neuromuscular junction in mice with amyotrophic lateral sclerosis","volume":"77","author":"Hurtado","year":"2020","journal-title":"Cell. Mol. Life Sci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/17\/1571\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:30:47Z","timestamp":1788150647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/17\/1571"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,29]]},"references-count":167,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cells15171571"],"URL":"https:\/\/doi.org\/10.3390\/cells15171571","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,29]]}}}