{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T02:30:09Z","timestamp":1776479409655,"version":"3.51.2"},"reference-count":57,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health grants NIA","award":["AG044486"],"award-info":[{"award-number":["AG044486"]}]},{"name":"National Institute of Health grants NIA","award":["AG015379"],"award-info":[{"award-number":["AG015379"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Glutamate transporter-1 (GLT-1) dynamics are implicated in excitotoxicity and Alzheimer\u2019s disease (AD) progression. Early stages of AD are often marked by hyperactivity and increased epileptiform activity preceding cognitive decline. Previously, we identified a direct interaction between GLT-1 and Presenilin 1 (PS1) in the brain, highlighting GLT-1 as a promising target in AD research. This study reports the significance of this interaction and uncovers a novel role of GLT-1 in modulating amyloid-beta (A\u03b2) production. Overexpression of GLT-1 in cells reduces the levels of A\u03b240 and A\u03b242 by decreasing \u03b3-secretase activity pertinent to APP processing and induces a more \u201copen\u201d PS1 conformation, resulting in decreased A\u03b242\/40 ratio. Inhibition of the GLT-1\/PS1 interaction using cell-permeable peptides produced an opposing effect on A\u03b2, highlighting the pivotal role of this interaction in regulating A\u03b2 levels. These findings emphasize the potential of targeting the GLT-1\/PS1 interaction as a novel therapeutic strategy for AD.<\/jats:p>","DOI":"10.3390\/cells13191600","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T08:54:17Z","timestamp":1727168057000},"page":"1600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Glutamate Transporter 1 as a Novel Negative Regulator of Amyloid \u03b2"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-7429","authenticated-orcid":false,"given":"Priyanka","family":"Sinha","sequence":"first","affiliation":[{"name":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuliia","family":"Turchyna","sequence":"additional","affiliation":[{"name":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shane Patrick Clancy","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1532-6613","authenticated-orcid":false,"given":"Michael","family":"Sadek","sequence":"additional","affiliation":[{"name":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3093-0092","authenticated-orcid":false,"given":"Gokce","family":"Armagan","sequence":"additional","affiliation":[{"name":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9273-1772","authenticated-orcid":false,"given":"Florian","family":"Perrin","sequence":"additional","affiliation":[{"name":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1970-2462","authenticated-orcid":false,"given":"Masato","family":"Maesako","sequence":"additional","affiliation":[{"name":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4898-5788","authenticated-orcid":false,"given":"Oksana","family":"Berezovska","sequence":"additional","affiliation":[{"name":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/nm.2460","article-title":"Resolving controversies on the path to Alzheimer\u2019s therapeutics","volume":"17","author":"Selkoe","year":"2011","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","article-title":"The Amyloid-\u03b2 Pathway in Alzheimer\u2019s Disease","volume":"26","author":"Hampel","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41392-023-01484-7","article-title":"Amyloid \u03b2-based therapy for Alzheimer\u2019s disease: Challenges, successes and future","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tamagno, E., Guglielmotto, M., Vasciaveo, V., and Tabaton, M. (2021). Oxidative Stress and Beta Amyloid in Alzheimer\u2019s Disease. Which Comes First: The Chicken or the Egg?. Antioxidants, 10.","DOI":"10.3390\/antiox10091479"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Di Benedetto, G., Burgaletto, C., Bellanca, C.M., Munaf\u00f2, A., Bernardini, R., and Cantarella, G. (2022). Role of Microglia and Astrocytes in Alzheimer\u2019s Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation. Cells, 11.","DOI":"10.3390\/cells11172728"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1038\/s41467-020-16074-2","article-title":"Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer\u2019s disease","volume":"11","author":"Hou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The Amyloid Hypothesis of Alzheimer\u2019s Disease: Progress and Problems on the Road to Therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12081","DOI":"10.1523\/JNEUROSCI.3614-06.2006","article-title":"Structure of the Catalytic Pore of \u03b3-Secretase Probed by the Accessibility of Substituted Cysteines","volume":"26","author":"Sato","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1750-1326-6-15","article-title":"Reciprocal relationship between APP positioning relative to the membrane and PS1 conformation","volume":"6","author":"Uemura","year":"2011","journal-title":"Mol. Neurodegener."},{"key":"ref_10","first-page":"589","article-title":"The dynamic conformational landscape of \u03b3-secretase","volume":"128","author":"Elad","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yang, F., Chen, L., Yu, Y., Xu, T., Chen, L., Yang, W., Wu, Q., and Han, Y. (2022). Alzheimer\u2019s disease and epilepsy: An increasingly recognized comorbidity. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.940515"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"109640","DOI":"10.1016\/j.yebeh.2024.109640","article-title":"The crosstalk between epilepsy and dementia: A systematic review and meta-analysis","volume":"152","author":"Chen","year":"2024","journal-title":"Epilepsy Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.14581\/jer.23009","article-title":"Aphasic Status Epilepticus Associated with Alzheimer\u2019s Disease: Clinical and Electrographic Characteristics","volume":"13","author":"Lee","year":"2023","journal-title":"J. Epilepsy Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13195-023-01373-9","article-title":"Subclinical epileptiform activity in the Alzheimer continuum: Association with disease, cognition and detection method","volume":"16","author":"Nous","year":"2024","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Vicente, M., Addo-Osafo, K., and Vossel, K. (2024). Latest advances in mechanisms of epileptic activity in Alzheimer\u2019s disease and dementia with Lewy Bodies. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1277613"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kalyvas, A.-C., Dimitriou, M., Ioannidis, P., Grigoriadis, N., and Afrantou, T. (2024). Alzheimer\u2019s Disease and Epilepsy: Exploring Shared Pathways and Promising Biomarkers for Future Treatments. J. Clin. Med., 13.","DOI":"10.3390\/jcm13133879"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2259","DOI":"10.1212\/WNL.0000000000010612","article-title":"Association of epileptiform abnormalities and seizures in Alzheimer disease","volume":"95","author":"Lam","year":"2020","journal-title":"Neurology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jfma.2015.08.004","article-title":"A systematic review of familial Alzheimer\u2019s disease: Differences in presentation of clinical features among three mutated genes and potential ethnic differences","volume":"115","author":"Shea","year":"2016","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S1474-4422(17)30044-3","article-title":"Epileptic activity in Alzheimer\u2019s disease: Causes and clinical relevance","volume":"16","author":"Vossel","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"0418","DOI":"10.1523\/ENEURO.0418-20.2020","article-title":"Neuronal Network Excitability in Alzheimer\u2019s Disease: The Puzzle of Similar versus Divergent Roles of Amyloid \u03b2 and Tau","volume":"8","author":"Kazim","year":"2021","journal-title":"eNeuro"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1001\/archneurol.2009.15","article-title":"Epilepsy and Cognitive Impairments in Alzheimer Disease","volume":"66","author":"Palop","year":"2009","journal-title":"Arch. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3453","DOI":"10.1523\/JNEUROSCI.5215-08.2009","article-title":"Amyloid \u03b2-Induced Neuronal Hyperexcitability Triggers Progressive Epilepsy","volume":"29","author":"Minkeviciene","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1001\/jamaneurol.2013.136","article-title":"Seizures and Epileptiform Activity in the Early Stages of Alzheimer Disease","volume":"70","author":"Vossel","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1002\/ana.24794","article-title":"Incidence and impact of subclinical epileptiform activity in Alzheimer\u2019s disease","volume":"80","author":"Vossel","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1001\/jamaneurol.2021.3310","article-title":"Effect of Levetiracetam on Cognition in Patients with Alzheimer Disease with and Without Epileptiform Activity","volume":"78","author":"Vossel","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gautam, D., Naik, U.P., Naik, M.U., Yadav, S.K., Chaurasia, R.N., and Dash, D. (2023). Glutamate Receptor Dysregulation and Platelet Glutamate Dynamics in Alzheimer\u2019s and Parkinson\u2019s Diseases: Insights into Current Medications. Biomolecules, 13.","DOI":"10.3390\/biom13111609"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8740","DOI":"10.1073\/pnas.1206171109","article-title":"Critical role of soluble amyloid-\u03b2 for early hippocampal hyperactivity in a mouse model of Alzheimer\u2019s disease","volume":"109","author":"Busche","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nrn.2016.141","article-title":"Network abnormalities and interneuron dysfunction in Alzheimer disease","volume":"17","author":"Palop","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"771","DOI":"10.3233\/JAD-142160","article-title":"Altered Neurotransmission Prior to Cognitive Decline in A\u03b2PP\/PS1 Mice, a Model of Alzheimer\u2019s Disease","volume":"44","author":"Hascup","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1471-4159.2006.04030.x","article-title":"GLT-1 down-regulation induced by clozapine in rat frontal cortex is associated with synaptophysin up-regulation","volume":"99","author":"Bragina","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3233\/JAD-2011-110503","article-title":"GLT-1 Loss Accelerates Cognitive Deficit Onset in an Alzheimer\u2019s Disease Animal Model","volume":"26","author":"Mookherjee","year":"2011","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1007\/s11064-022-03699-6","article-title":"A\u00df Pathology and Neuron\u2013Glia Interactions: A Synaptocentric View","volume":"48","author":"Huffels","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3233\/JAD-142304","article-title":"Partial Loss of the Glutamate Transporter GLT-1 Alters Brain Akt and Insulin Signaling in a Mouse Model of Alzheimer\u2019s Disease","volume":"45","author":"Meeker","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gao, J., Liu, L., Liu, C., Fan, S., Liu, L., Liu, S., Xian, X.-H., and Li, W.-B. (2020). GLT-1 Knockdown Inhibits Ceftriaxone-Mediated Improvements on Cognitive Deficits, and GLT-1 and xCT Expression and Activity in APP\/PS1 AD Mice. Front. Aging Neurosci., 12.","DOI":"10.3389\/fnagi.2020.580772"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5312","DOI":"10.1523\/JNEUROSCI.5274-12.2013","article-title":"Amyloid-\u03b21\u201342Slows Clearance of Synaptically Released Glutamate by Mislocalizing Astrocytic GLT-1","volume":"33","author":"Scimemi","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bukke, V.N., Archana, M., Villani, R., Romano, A.D., Wawrzyniak, A., Balawender, K., Orkisz, S., Beggiato, S., Serviddio, G., and Cassano, T. (2020). The Dual Role of Glutamatergic Neurotransmission in Alzheimer\u2019s Disease: From Pathophysiology to Pharmacotherapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207452"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zoltowska, K.M., Maesako, M., Meier, J., and Berezovska, O. (2018). Novel interaction between Alzheimer\u2019s disease-related protein presenilin 1 and glutamate transporter 1. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-26888-2"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Perrin, F., Sinha, P., Mitchell, S.P.C., Sadek, M., Maesako, M., and Berezovska, O. (2024). Identification of PS1\/gamma-secretase and glutamate transporter GLT-1 interaction sites. J. Biol. Chem., 300.","DOI":"10.1101\/2023.05.30.542955"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Houser, M.C., Hou, S.S., Perrin, F., Turchyna, Y., Bacskai, B.J., Berezovska, O., and Maesako, M. (2020). A Novel NIR-FRET Biosensor for Reporting PS\/\u03b3-Secretase Activity in Live Cells. Sensors, 20.","DOI":"10.3390\/s20215980"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lehmann, S., Delaby, C., Boursier, G., Catteau, C., Ginestet, N., Tiers, L., Maceski, A., Navucet, S., Paquet, C., and Dumurgier, J. (2018). Relevance of A\u03b242\/40 Ratio for Detection of Alzheimer Disease Pathology in Clinical Routine: The PLMR Scale. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00138"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Uemura, K., Lill, C.M., Li, X., Peters, J.A., Ivanov, A., Fan, Z., DeStrooper, B., Bacskai, B.J., Hyman, B.T., and Berezovska, O. (2009). Allosteric Modulation of PS1\/\u03b3-Secretase Conformation Correlates with Amyloid \u03b242\/40 Ratio. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007893"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1084\/jem.20140413","article-title":"Restored glial glutamate transporter EAAT2 function as a potential therapeutic approach for Alzheimer\u2019s disease","volume":"212","author":"Takahashi","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.neurobiolaging.2018.08.002","article-title":"Altered glutamate clearance in ascorbate deficient mice increases seizure susceptibility and contributes to cognitive impairment in APP\/PSEN1 mice","volume":"71","author":"Mi","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1523\/JNEUROSCI.0364-05.2005","article-title":"Familial Alzheimer\u2019s Disease Presenilin 1 Mutations Cause Alterations in the Conformation of Presenilin and Interactions with Amyloid Precursor Protein","volume":"25","author":"Berezovska","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8600","DOI":"10.1523\/JNEUROSCI.0838-19.2019","article-title":"Conformational Dynamics of Transmembrane Domain 3 of Presenilin 1 Is Associated with the Trimming Activity of \u03b3-Secretase","volume":"39","author":"Cai","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1074\/jbc.M113.498246","article-title":"Characterization of Intermediate Steps in Amyloid Beta (A\u03b2) Production under Near-native Conditions","volume":"289","author":"Olsson","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cell.2017.07.004","article-title":"Alzheimer\u2019s-Causing Mutations Shift A\u03b2 Length by Destabilizing \u03b3-Secretase-A\u03b2n Interactions","volume":"170","author":"Szaruga","year":"2017","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1002\/ana.410400512","article-title":"Deficient glutamate tranport is associated with neurodegeneration in Alzheimer\u2019s disease","volume":"40","author":"Masliah","year":"1996","journal-title":"Ann. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Kobayashi, E., Nakano, M., Kubota, K., Himuro, N., Mizoguchi, S., Chikenji, T., Otani, M., Mizue, Y., Nagaishi, K., and Fujimiya, M. (2018). Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-19442-7"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Perrin, F., Anderson, L.C., Mitchell, S.P.C., Sinha, P., Turchyna, Y., Maesako, M., Houser, M.C.Q., Zhang, C., Wagner, S.L., and Tanzi, R.E. (2023). PS1\/gamma-secretase acts as rogue chaperone of glutamate transporter EAAT2\/GLT-1 in Alzheimer\u2019s disease. Research Square.","DOI":"10.21203\/rs.3.rs-3495211\/v1"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/0896-6273(94)90038-8","article-title":"Localization of neuronal and glial glutamate transporters","volume":"13","author":"Rothstein","year":"1994","journal-title":"Neuron"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Rimmele, T.S., Li, S., Andersen, J.V., Westi, E.W., Rotenberg, A., Wang, J., Aldana, B.I., Selkoe, D.J., Aoki, C.J., and Dulla, C.G. (2021). Neuronal Loss of the Glutamate Transporter GLT-1 Promotes Excitotoxic Injury in the Hippocampus. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.788262"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"107559","DOI":"10.1016\/j.neuropharm.2019.03.002","article-title":"The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: Potential targets for neurotherapeutics","volume":"161","author":"Pajarillo","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"108719","DOI":"10.1016\/j.neuropharm.2021.108719","article-title":"Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration","volume":"196","author":"Andersen","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13024-017-0159-y","article-title":"Dynamic presenilin 1 and synaptotagmin 1 interaction modulates exocytosis and amyloid \u03b2 production","volume":"12","author":"Zoltowska","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Sun, Y., Islam, S., Michikawa, M., and Zou, K. (2024). Presenilin: A Multi-Functional Molecule in the Pathogenesis of Alzheimer\u2019s Disease and Other Neurodegenerative Diseases. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031757"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1016\/j.stemcr.2017.10.016","article-title":"PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer\u2019s Disease","volume":"9","author":"Oksanen","year":"2017","journal-title":"Stem Cell Rep."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/19\/1600\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:01:18Z","timestamp":1760112078000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/19\/1600"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,24]]},"references-count":57,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["cells13191600"],"URL":"https:\/\/doi.org\/10.3390\/cells13191600","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,24]]}}}