{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:24:40Z","timestamp":1792016680556,"version":"4.4.0"},"reference-count":100,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"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":"publisher","award":["62171457"],"award-info":[{"award-number":["62171457"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["20BJZ49"],"award-info":[{"award-number":["20BJZ49"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Logistics Research Program","award":["62171457"],"award-info":[{"award-number":["62171457"]}]},{"name":"Logistics Research Program","award":["20BJZ49"],"award-info":[{"award-number":["20BJZ49"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most frequent cause of cognitive impairment in middle-aged and older populations. There is a lack of drugs that demonstrate significant efficacy in AD, so the study of the pathogenesis of AD is of great importance. More efficacious interventions are needed, as reflected by our population\u2019s fast aging. Synaptic plasticity is the capacity of neurons to adjust their connections, and it is strongly tied to learning and memory, cognitive function, and brain injury recovery. Changes in synaptic strength, such as long-term potentiation (LTP) or inhibition (LTD), are thought to represent the biological foundation of the early stages of learning and memory. The results of numerous studies confirm that neurotransmitters and their receptors play an important role in the regulation of synaptic plasticity. However, so far, there is no definite correlation between the function of neurotransmitters in aberrant neural oscillation and AD-related cognitive impairment. We summarized the AD process to understand the impact of neurotransmitters in the progression and pathogenesis of AD, including the current status of neurotransmitter target drugs, and the latest evidence of neurotransmitters\u2019 function and changes in the AD process.<\/jats:p>","DOI":"10.3390\/ijms24043841","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T02:31:23Z","timestamp":1676428283000},"page":"3841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Neurotransmitters in Prevention and Treatment of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Zhenqi","family":"Yang","sequence":"first","affiliation":[{"name":"Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zou","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.3233\/JAD-161118","article-title":"Therapeutics of Neurotransmitters in Alzheimer\u2019s Disease","volume":"57","author":"Kandimalla","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108122","DOI":"10.1016\/j.pharmthera.2022.108122","article-title":"Arumugam, Dong-Gyu Jo, Physiology and pharmacology of amyloid precursor protein","volume":"235","author":"Cho","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_3","first-page":"701","article-title":"The link between C-reactive protein and Alzheimer\u2019s disease among mexican Americans","volume":"34","author":"Johnson","year":"2012","journal-title":"J. Alzheimer\u2019s Dis. Jad"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1126\/science.aay0198","article-title":"A vicious cycle of \u03b2 amyloid-dependent neuronal hyperactivation","volume":"365","author":"Zott","year":"2019","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1080\/13543784.2019.1619694","article-title":"Tau immunotherapies for Alzheimer\u2019s disease","volume":"28","author":"Hoskin","year":"2019","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.neuron.2018.01.022","article-title":"Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau","volume":"97","author":"McInnes","year":"2018","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"572308","DOI":"10.3389\/fnmol.2020.572308","article-title":"The Role of Copper in Tau-Related Pathology in Alzheimer\u2019s Disease","volume":"13","author":"Hof","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"671779","DOI":"10.3389\/fnmol.2021.671779","article-title":"Dendritic\/Post-synaptic Tau and Early Pathology of Alzheimer\u2019s Disease","volume":"14","author":"Yin","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s00401-019-02053-5","article-title":"A\u03b2-induced acceleration of Alzheimer-related \u03c4-pathology spreading and its association with prion protein","volume":"138","author":"Gomes","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1093\/brain\/awz035","article-title":"In vivo imaging reveals reduced activity of neuronal circuits in a mouse tauopathy model","volume":"142","author":"Blumenstock","year":"2019","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41593-018-0289-8","article-title":"Tau impairs neural circuits, dominating amyloid-\u03b2 effects, in Alzheimer models in vivo","volume":"22","author":"Busche","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"660","DOI":"10.3389\/fnins.2020.00660","article-title":"GABAergic Inhibitory Interneuron Deficits in Alzheimer\u2019s Disease: Implications for Treatment","volume":"14","author":"Xu","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.clinbiochem.2019.04.001","article-title":"Neuro-inflammation and anti-inflammatory treatment options for Alzheimer\u2019s disease","volume":"72","author":"Ozben","year":"2019","journal-title":"Clin. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1586\/14737175.2015.988709","article-title":"Pharmacological approaches for Alzheimer\u2019s disease: Neurotransmitter as drug targets","volume":"15","author":"Prakash","year":"2015","journal-title":"Expert Rev. Neurother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/jnr.24116","article-title":"Calcium dependence of spontaneous neurotransmitter release","volume":"96","author":"Williams","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107556","DOI":"10.1016\/j.neuropharm.2019.02.038","article-title":"Dynamic compartmentalization of calcium channel signalling in neurons","volume":"169","author":"Heine","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1093\/brain\/awy132","article-title":"The cholinergic system in the pathophysiology and treatment of Alzheimer\u2019s disease","volume":"141","author":"Hampel","year":"2018","journal-title":"Brain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"660342","DOI":"10.3389\/fimmu.2021.660342","article-title":"Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity","volume":"12","author":"Halder","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19942","DOI":"10.1074\/jbc.M902174199","article-title":"Phosphorylation of the rat vesicular acetylcholine transporter","volume":"275","author":"Cho","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"114381","DOI":"10.1016\/j.ab.2021.114381","article-title":"An overview of recent analysis and detection of acetylcholine","volume":"632","author":"Gu","year":"2021","journal-title":"Anal. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2174\/1570159X13666150716165726","article-title":"Alzheimer\u2019s disease: Targeting the Cholinergic System","volume":"14","author":"Guimaraes","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14442","DOI":"10.1523\/JNEUROSCI.4104-07.2007","article-title":"Focusing effect of acetylcholine on neuroplasticity in the human motor cortex","volume":"27","author":"Kuo","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.npep.2015.06.008","article-title":"Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer\u2019s disease","volume":"52","author":"Barage","year":"2015","journal-title":"Neuropeptides"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/jnc.14052","article-title":"Cholinergic modulation of the hippocampal region and memory function","volume":"142","author":"Haam","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-3-030-32633-3_15","article-title":"Alzheimer\u2019s Disease Therapeutic Approaches","volume":"1195","author":"Revi","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1523\/JNEUROSCI.1470-21.2021","article-title":"Synaptic Input and ACh Modulation Regulate Dendritic Ca2+ Spike Duration in Pyramidal Neurons, Directly Affecting Their Somatic OutputAmir Dudai, Michael Doron, Idan Segev, Michael London","volume":"42","author":"Dudai","year":"2022","journal-title":"J. Neurosci."},{"key":"ref_27","first-page":"1479","article-title":"Cholinesterase inhibitors as Alzheimer\u2019s therapeutics (Review)","volume":"20","author":"Sharma","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9148650","DOI":"10.1155\/2022\/9148650","article-title":"Effect of Resveratrol Combined with Donepezil Hydrochloride on Inflammatory Factor Level and Cognitive Function Level of Patients with Alzheimer\u2019s Disease","volume":"2022","author":"Fang","year":"2022","journal-title":"J. Healthc. Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1192\/j.eurpsy.2021.8","article-title":"Quantifying the heterogeneity of cognitive functioning in Alzheimer\u2019s disease to extend the placebo-treatment dichotomy: Latent class analysis of individual-participant data from five pivotal randomized clinical trials of donepezil","volume":"64","author":"Levine","year":"2021","journal-title":"Eur. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3233\/JAD-190940","article-title":"Safety and Efficacy of Donepezil 10 mg\/day in Patients with Mild to Moderate Alzheimer\u2019s Disease","volume":"74","author":"Jia","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"108352","DOI":"10.1016\/j.neuropharm.2020.108352","article-title":"Efficacy of acetylcholinesterase inhibitors in Alzheimer\u2019s disease","volume":"190","author":"Marucci","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.2147\/NDT.S133145","article-title":"Long-term effect of galantamine on cognitive function in patients with Alzheimer\u2019s disease versus a simulated disease trajectory: An observational study in the clinical setting","volume":"13","author":"Nakagawa","year":"2017","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/ane.12195","article-title":"Galantamine treatment in outpatients with mild Alzheimer\u2019s disease","volume":"129","author":"Richarz","year":"2014","journal-title":"Acta Neurol. Scand."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/cns.12158","article-title":"A 24-week, randomized, controlled trial of rivastigmine patch 13.3 mg\/24 h versus 4.6 mg\/24 h in severe Alzheimer\u2019s dementia","volume":"19","author":"Farlow","year":"2013","journal-title":"CNS Neurosci Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/cns.12385","article-title":"Evaluating Response to High-Dose 13.3 mg\/24 h Rivastigmine Patch in Patients with Severe Alzheimer\u2019s Disease","volume":"21","author":"Farlow","year":"2015","journal-title":"CNS Neurosci. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e13037","DOI":"10.1111\/acel.13037","article-title":"Lifelong choline supplementation ameliorates Alzheimer\u2019s disease pathology and associated cognitive deficits by attenuating microglia activation","volume":"18","author":"Velazquez","year":"2019","journal-title":"Aging Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.1007\/s00213-021-05942-4","article-title":"Potentiation of cognitive enhancer effects of Alzheimer\u2019s disease medication memantine by alpha7 nicotinic acetylcholine receptor agonist PHA-543613 in the Morris water maze task","volume":"238","author":"Bruszt","year":"2021","journal-title":"Psychopharmacology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12929-017-0355-7","article-title":"Drug candidates in clinical trials for Alzheimer\u2019s disease","volume":"24","author":"Hung","year":"2017","journal-title":"J. Biomed. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1111\/jgs.14827","article-title":"Adherence and Tolerability of Alzheimer\u2019s Disease Medications: A Pragmatic Randomized Trial","volume":"65","author":"Campbell","year":"2017","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"l6930","DOI":"10.1136\/bmj.l6930","article-title":"France removes state funding for dementia drugs","volume":"367","author":"Walsh","year":"2019","journal-title":"BMJ"},{"key":"ref_41","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_42","doi-asserted-by":"crossref","unstructured":"Mahmoud, S., Gharagozloo, M., Simard, C., and Gris, D. (2019). Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release. Cells, 8.","DOI":"10.3390\/cells8020184"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lira, M., Mira, R.G., Carvajal, F.J., Zamorano, P., Inestrosa, N.C., and Cerpa, W. (2020). Glutamatergic Receptor Trafficking and Delivery: Role of the Exocyst Complex. Cells, 9.","DOI":"10.3390\/cells9112402"},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/jnc.14046","article-title":"Functional identification of activity-regulated, high-affinity glutamine transport in hippocampal neurons inhibited by riluzole","volume":"142","author":"Erickson","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/j.neuron.2018.05.018","article-title":"Glutamatergic Signaling in the Central Nervous System: Ionotropic and Metabotropic Receptors in Concert","volume":"98","author":"Reiner","year":"2018","journal-title":"Neuron"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1124\/pr.109.002451","article-title":"Glutamate receptor ion channels: Structure, regulation, and function","volume":"62","author":"Traynelis","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.pnpbp.2017.09.014","article-title":"Glutamatergic synapses in neurodevelopmental disorders","volume":"84 Pt B","author":"Moretto","year":"2018","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"108540","DOI":"10.1016\/j.neuropharm.2021.108540","article-title":"Kainate receptors and synaptic plasticity","volume":"1","author":"Nair","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.phrs.2016.11.013","article-title":"Metabotropic glutamate receptors and neurodegenerative diseases","volume":"115","author":"Ribeiro","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s10522-020-09860-4","article-title":"Alzheimer\u2019s disease: Targeting the glutamatergic system","volume":"21","author":"Conway","year":"2020","journal-title":"Biogerontology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.3233\/JAD-190773","article-title":"Reduced Hippocampal Glutamate and Posterior Cingulate N-Acetyl Aspartate in Mild Cognitive Impairment and Alzheimer\u2019s Disease Is Associated with Episodic Memory Performance and White Matter Integrity in the Cingulum: A Pilot Study","volume":"73","author":"Dickson","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1007\/s12031-020-01747-w","article-title":"Hippocampal Degeneration and Behavioral Impairment During Alzheimer-Like Pathogenesis Involves Glutamate Excitotoxicity","volume":"71","author":"Olajide","year":"2021","journal-title":"J. Mol. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"957","DOI":"10.3233\/JAD-190274","article-title":"Oral Monosodium Glutamate Administration Causes Early Onset of Alzheimer\u2019s Disease-Like Pathophysiology in APP\/PS1 Mice","volume":"72","author":"Fuchsberger","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.1007\/s11033-020-05438-y","article-title":"Memory-related process in physiological status and alzheimer\u2019s disease","volume":"47","author":"Fotuhi","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.neures.2020.04.004","article-title":"Proteomic analysis involved with synaptic plasticity improvement by GABAA receptor blockade in hippocampus of a mouse model of Alzheimer\u2019s disease","volume":"165","author":"Kadoyama","year":"2021","journal-title":"Neurosci. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.bbr.2008.02.016","article-title":"Selkoe, Soluble oligomers of the amyloid \u03b2-protein impair synaptic plasticity and behavior","volume":"192","author":"Dennis","year":"2008","journal-title":"Behav. Brain Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3233\/JAD-170424","article-title":"Memantine for Alzheimer\u2019s Disease: An Updated Systematic Review and Meta-analysis","volume":"60","author":"Kishi","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1001\/jama.291.3.317","article-title":"Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: A randomized controlled trial","volume":"291","author":"Tariot","year":"2004","journal-title":"JAMA"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Li, P., Xu, J., Gu, H., Peng, H., Yin, Y., and Zhuang, J. (2021). Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal\u2013CA1 projection. BMC Neurosci., 22.","DOI":"10.1186\/s12868-021-00647-y"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1080\/14740338.2022.2071867","article-title":"A review of potential neuropathological changes associated with ketamine","volume":"21","author":"Nogo","year":"2022","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.biopsych.2021.02.970","article-title":"Activating mGlu3 Metabotropic Glutamate Receptors Rescues Schizophrenia-like Cognitive Deficits Through Metaplastic Adaptations Within the Hippocampus","volume":"90","author":"Dogra","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/bs.apha.2019.03.004","article-title":"mGlu2\/3 receptor antagonists","volume":"86","author":"Chaki","year":"2019","journal-title":"Adv. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.tips.2018.04.003","article-title":"An Emerging Circuit Pharmacology of GABAA Receptors","volume":"39","author":"Engin","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.neuint.2012.02.013","article-title":"Glutamate and GABA synthesis, release, transport and metabolism as targets for seizure control","volume":"61","author":"Rowley","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/j.1471-4159.2006.03913.x","article-title":"The glutamate\/GABA-glutamine cycle: Aspects of transport, neurotransmitter homeostasis and ammonia transfer","volume":"98","author":"Bak","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"834498","DOI":"10.3389\/fmolb.2022.834498","article-title":"Molecular and Clinical Repercussions of GABA Transporter 1 Variants Gone Amiss: Links to Epilepsy and Developmental Spectrum Disorders","volume":"9","author":"Fischer","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s43141-021-00224-0","article-title":"GABAA receptors: Structure, function, pharmacology, and related disorders","volume":"19","author":"Ghit","year":"2021","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nrn3249","article-title":"Regulation of neuronal GABAB receptor functions by subunit composition","volume":"13","author":"Gassmann","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1007\/s11064-021-03276-3","article-title":"Downregulation of GABA Transporter 3 (GAT3) is Associated with Deficient Oxidative GABA Metabolism in Human Induced Pluripotent Stem Cell-Derived Astrocytes in Alzheimer\u2019s Disease","volume":"46","author":"Salcedo","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.neurobiolaging.2020.10.013","article-title":"Alterations of GABA B receptors in the APP\/PS1 mouse model of Alzheimer\u2019s disease","volume":"97","author":"Salazar","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.stem.2019.12.015","article-title":"Interneuron Accumulation of Phosphorylated tau Impairs Adult Hippocampal Neurogenesis by Suppressing GABAergic Transmission","volume":"26","author":"Zheng","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.neuint.2009.01.020","article-title":"A novel mechanism for GABA synthesis and packaging into synaptic vesicles","volume":"55","author":"Buddhala","year":"2009","journal-title":"Neurochem. Int."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Dade, M., Berzero, G., Izquierdo, C., Giry, M., Benazra, M., Delattre, J.Y., Psimaras, D., and Alentorn, A. (2020). Neurological Syndromes Associated with Anti-GAD Antibodies. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103701"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.tins.2007.05.003","article-title":"Role of GABAergic inhibition in hippocampal network oscillations","volume":"30","author":"Mann","year":"2007","journal-title":"Trends Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.neuroscience.2018.02.014","article-title":"Cell Type-specific Intrinsic Perithreshold Oscillations in Hippocampal GABAergic Interneurons","volume":"376","author":"Kang","year":"2018","journal-title":"Neuroscience"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Hollnagel, J.O., Elzoheiry, S., Gorgas, K., Kins, S., Beretta, C.A., Kirsch, J., Kuhse, J., Kann, O., and Kiss, E. (2019). Early alterations in hippocampal perisomatic GABAergic synapses and network oscillations in a mouse model of Alzheimer\u2019s disease amyloidosis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0209228"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"837","DOI":"10.3233\/JAD-210041","article-title":"TREM2 Deficiency Disrupts Network Oscillations Leading to Epileptic Activity and Aggravates Amyloid-\u03b2-Related Hippocampal Pathophysiology in Mice","volume":"88","author":"Stoiljkovic","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"101878","DOI":"10.1016\/j.pneurobio.2020.101878","article-title":"Neural oscillations and brain stimulation in Alzheimer\u2019s disease","volume":"194","author":"Jafari","year":"2020","journal-title":"Prog. Neurobiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nature20587","article-title":"Gamma frequency entrainment attenuates amyloid load and modifies microglia","volume":"540","author":"Iaccarino","year":"2016","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neurobiolaging.2020.05.002","article-title":"Early-stage dysfunction of hippocampal theta and gamma oscillations and its modulation of neural network in a transgenic 5xFAD mouse model","volume":"94","author":"Wang","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/aps.2017.172","article-title":"GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia","volume":"39","author":"Xu","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"9350","DOI":"10.1523\/JNEUROSCI.0335-21.2021","article-title":"Dynamic Recovery: GABA Agonism Restores Neural Variability in Older, Poorer Performing Adults","volume":"41","author":"Lalwani","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Roth, W., Zadeh, K., Vekariya, R., Ge, Y., and Mohamadzadeh, M. (2021). Tryptophan Metabolism and Gut-Brain Homeostasis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062973"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"108155","DOI":"10.1016\/j.neuropharm.2020.108155","article-title":"Central 5-HT receptors and their function; present and future","volume":"177","author":"Harp","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Voronova, I.P. (2021). 5-HT Receptors and Temperature Homeostasis. Biomolecules, 11.","DOI":"10.3390\/biom11121914"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.conb.2019.01.001","article-title":"Mechanisms and regulation of dopamine release","volume":"57","author":"Liu","year":"2019","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10571-018-0632-3","article-title":"Dopamine: Functions, Signaling, and Association with Neurological Diseases","volume":"39","author":"Klein","year":"2019","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.3389\/fphar.2020.01003","article-title":"Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia","volume":"11","author":"Martel","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"108118","DOI":"10.1016\/j.neuropharm.2020.108118","article-title":"Opportunities for multiscale computational modelling of serotonergic drug effects in Alzheimer\u2019s disease","volume":"174","author":"Joshi","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.3233\/JAD-160601","article-title":"How Studies of the Serotonin System in Macaque Models of Menopause Relate to Alzheimer\u2019s Disease1","volume":"57","author":"Bethea","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"483","DOI":"10.3389\/fphar.2019.00483","article-title":"Monoaminergic System Modulation in Depression and Alzheimer\u2019s Disease: A New Standpoint?","volume":"10","author":"Morgese","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.neuroscience.2017.06.034","article-title":"Newly Developed Drugs for Alzheimer\u2019s Disease in Relation to Energy Metabolism, Cholinergic and Monoaminergic Neurotransmission","volume":"370","year":"2018","journal-title":"Neuroscience"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1093\/hmg\/ddab054","article-title":"Protective effects of antidepressant citalopram against abnormal APP processing and amyloid beta-induced mitochondrial dynamics, biogenesis, mitophagy and synaptic toxicities in Alzheimer\u2019s disease","volume":"30","author":"Reddy","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.neuropharm.2011.02.026","article-title":"5-HT (4) receptor agonist mediated enhancement of cognitive function in vivo and amyloid precursor protein processing in vitro: A pharmacodynamic and pharmacokinetic assessment","volume":"61","author":"Shen","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.redox.2018.01.008","article-title":"13 reasons why the brain is susceptible to oxidative stress","volume":"15","author":"Cobley","year":"2018","journal-title":"Redox Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3389\/fendo.2020.00319","article-title":"Mitochondrial Bioenergetics and Dynamics in Secretion Processes","volume":"11","author":"Marmisolle","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.freeradbiomed.2016.11.045","article-title":"Adaptive responses of neuronal mitochondria to bioenergetic challenges: Roles in neuroplasticity and disease resistance","volume":"102","author":"Raefsky","year":"2017","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"111216","DOI":"10.1016\/j.mad.2020.111216","article-title":"Regulation and roles of mitophagy at synapses","volume":"187","author":"Palikaras","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1111\/bph.14585","article-title":"Mitochondrial dysfunction in Alzheimer\u2019s disease: Role in pathogenesis and novel therapeutic opportunities","volume":"176","author":"Swerdlow","year":"2019","journal-title":"Br. J. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3841\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:35:26Z","timestamp":1760121326000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,14]]},"references-count":100,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043841"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043841","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,14]]}}}