{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T12:18:07Z","timestamp":1772540287202,"version":"3.50.1"},"reference-count":70,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:00:00Z","timestamp":1696291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-74-20176"],"award-info":[{"award-number":["19-74-20176"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["075-15-2021-1067"],"award-info":[{"award-number":["075-15-2021-1067"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["19-74-20176"],"award-info":[{"award-number":["19-74-20176"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2021-1067"],"award-info":[{"award-number":["075-15-2021-1067"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer disease (AD) is a widespread neurodegenerative disease characterized by the accumulation of oligomeric toxic forms of \u03b2-amyloid (A\u03b21-42) and dysfunction of the cholinergic system in the different brain regions. However, the exact mechanisms of AD pathogenesis and the role of the nicotinic acetylcholine receptors (nAChRs) in the disease progression remain unclear. Here, we revealed a decreased expression of a number of the Ly6\/uPAR proteins targeting nAChRs in the cerebellum of 2xTg-AD mice (model of early AD) in comparison with non-transgenic mice both at mRNA and protein levels. We showed that co-localization of one of them, \u2013 neuromodulator Lynx1, with \u03b17-nAChR was diminished in the vicinity of cerebellar astrocytes of 2xTg-AD mice, while A\u03b21-42 co-localization with this receptor present was increased. Moreover, the expression of anti-inflammatory transcription factor KLF4 regulating transcription of the Ly6\/uPAR genes was decreased in the cerebellum of 2xTg-AD mice, while expression of inflammatory cytokine TNF-\u03b1 was increased. Based on these data together with observed astrocyte degeneration in the cerebellum of 2xTg-AD mice, we suggest the mechanism by which expression of the Ly6\/uPAR proteins upon A\u03b2 pathology results in dysregulation of the cholinergic system and particularly of \u03b17-nAChR function in the cerebellum. This leads to enhanced neuroinflammation and cerebellar astrocyte degeneration.<\/jats:p>","DOI":"10.3390\/ijms241914852","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T07:28:29Z","timestamp":1696318109000},"page":"14852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A\u03b21-42 Accumulation Accompanies Changed Expression of Ly6\/uPAR Proteins, Dysregulation of the Cholinergic System, and Degeneration of Astrocytes in the Cerebellum of Mouse Model of Early Alzheimer Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Maxim L.","family":"Bychkov","sequence":"first","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9913-1842","authenticated-orcid":false,"given":"Aizek B.","family":"Isaev","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"},{"name":"Moscow Institute of Physics and Technology, State University, 141701 Dolgoprudny, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1173-8153","authenticated-orcid":false,"given":"Alexander A.","family":"Andreev-Andrievskiy","sequence":"additional","affiliation":[{"name":"Interdisciplinary Scientific and Educational School of Moscow University \u00abMolecular Technologies of the Living Systems and Synthetic Biology\u00bb, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Institute for Biomedical Problems of Russian Academy of Sciences, 123007 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantin","family":"Petrov","sequence":"additional","affiliation":[{"name":"Arbuzov Institute of Organic and Physical Chemistry, Federal Research Center \u201cKazan Scientific Center of the Russian Academy of Sciences\u201d, Arbuzov Str., 8, 420088 Kazan, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander S.","family":"Paramonov","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail P.","family":"Kirpichnikov","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"},{"name":"Interdisciplinary Scientific and Educational School of Moscow University \u00abMolecular Technologies of the Living Systems and Synthetic Biology\u00bb, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina N.","family":"Lyukmanova","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"},{"name":"Moscow Institute of Physics and Technology, State University, 141701 Dolgoprudny, Russia"},{"name":"Interdisciplinary Scientific and Educational School of Moscow University \u00abMolecular Technologies of the Living Systems and Synthetic Biology\u00bb, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Biological Department, Shenzhen MSU-BIT University, Shenzhen 518172, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,3]]},"reference":[{"key":"ref_1","unstructured":"(2022, November 01). Global Action Plan on the Public Health Response to Dementia 2017\u20132025. Available online: https:\/\/www.who.int\/publications-detail-redirect\/9789241513487."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e479","DOI":"10.1016\/S2666-7568(21)00140-9","article-title":"Mortality Rates in Alzheimer\u2019s Disease and Non-Alzheimer\u2019s Dementias: A Systematic Review and Meta-Analysis","volume":"2","author":"Liang","year":"2021","journal-title":"Lancet Healthy Longev."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1016\/j.ijbiomac.2020.07.327","article-title":"Role of Tau Protein in Alzheimer\u2019s Disease: The Prime Pathological Player","volume":"163","author":"Muralidar","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3389\/fncel.2019.00037","article-title":"Molecular Modulation of Human A7 Nicotinic Receptor by Amyloid-\u03b2 Peptides","volume":"13","author":"Lasala","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"25056","DOI":"10.1074\/jbc.M200066200","article-title":"Beta-Amyloid Peptide Activates Alpha 7 Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes","volume":"277","author":"Dineley","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"618","DOI":"10.2174\/15672050113109990132","article-title":"On the Interaction of \u03b2-Amyloid Peptides and A7-Nicotinic Acetylcholine Receptors in Alzheimer\u2019s Disease","volume":"10","author":"Oz","year":"2013","journal-title":"Curr. Alzheimer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/s41419-020-03020-9","article-title":"Intracellular Amyloid Toxicity Induces Oxytosis\/Ferroptosis Regulated Cell Death","volume":"11","author":"Huang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3389\/fncel.2019.00309","article-title":"Alzheimer\u2019s Disease as a Membrane Disorder: Spatial Cross-Talk Among Beta-Amyloid Peptides, Nicotinic Acetylcholine Receptors and Lipid Rafts","volume":"13","author":"Fabiani","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"841","DOI":"10.3233\/JAD-2012-121447","article-title":"Modulation of A7 Nicotinic Acetylcholine Receptor and Fibrillar Amyloid-\u03b2 Interactions in Alzheimer\u2019s Disease Brain","volume":"33","author":"Ni","year":"2013","journal-title":"J. Alzheimers Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1124\/pr.108.000562","article-title":"Nicotinic Acetylcholine Receptor Signalling: Roles in Alzheimer\u2019s Disease and Amyloid Neuroprotection","volume":"61","author":"Buckingham","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/brain\/awx194","article-title":"The Cerebellum in Alzheimer\u2019s Disease: Evaluating Its Role in Cognitive Decline","volume":"141","author":"Jacobs","year":"2018","journal-title":"Brain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.neulet.2018.07.005","article-title":"The Cerebellum and Cognition","volume":"688","author":"Schmahmann","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"102605","DOI":"10.1016\/j.nicl.2021.102605","article-title":"Differential Vulnerability of the Cerebellum in Healthy Ageing and Alzheimer\u2019s Disease","volume":"30","author":"Gellersen","year":"2021","journal-title":"Neuroimage Clin."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kulbatskii, D., Shenkarev, Z., Bychkov, M., Loktyushov, E., Shulepko, M., Koshelev, S., Povarov, I., Popov, A., Peigneur, S., and Chugunov, A. (2021). Human Three-Finger Protein Lypd6 Is a Negative Modulator of the Cholinergic System in the Brain. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.662227"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1134\/S1068162018060043","article-title":"Human Nicotinic Acetylcholine Receptors: Part I. Structure, Function, and Role in Neuromuscular Transmission and CNS Functioning","volume":"44","author":"Kulbatskii","year":"2018","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/jnc.15018","article-title":"Water-Soluble Variant of Human Lynx1 Positively Modulates Synaptic Plasticity and Ameliorates Cognitive Impairment Associated with A7-nAChR Dysfunction","volume":"155","author":"Shenkarev","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8461","DOI":"10.1523\/JNEUROSCI.0494-21.2021","article-title":"Unbalanced Regulation of A7 nAChRs by Ly6h and NACHO Contributes to Neurotoxicity in Alzheimer\u2019s Disease","volume":"41","author":"Wu","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lyukmanova, E., Shulepko, M., Kudryavtsev, D., Bychkov, M., Kulbatskii, D.S., Kasheverov, I., Astapova, M., Feofanov, A., Thomsen, M., and Mikkelsen, J. (2016). Human Secreted Ly-6\/uPAR Related Protein-1 (SLURP-1) Is a Selective Allosteric Antagonist of A7 Nicotinic Acetylcholine Receptor. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149733"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"30698","DOI":"10.1038\/srep30698","article-title":"Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of Interactions with Different Types of Acetylcholine Receptors","volume":"6","author":"Lyukmanova","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1073\/pnas.0813109106","article-title":"A Role for LYNX2 in Anxiety-Related Behavior","volume":"106","author":"Tekinay","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14847","DOI":"10.1523\/JNEUROSCI.2271-09.2009","article-title":"Prostate Stem Cell Antigen Is an Endogenous Lynx1-like Prototoxin That Antagonizes Alpha7-Containing Nicotinic Receptors and Prevents Programmed Cell Death of Parasympathetic Neurons","volume":"29","author":"Hruska","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1093\/carcin\/bgac003","article-title":"A5-nAChR Associated with Ly6E Modulates Cell Migration via TGF-\u03921\/Smad Signaling in Non-Small Cell Lung Cancer","volume":"43","author":"Zhang","year":"2022","journal-title":"Carcinogenesis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"24509","DOI":"10.1074\/jbc.M115.647248","article-title":"Mechanisms of Inhibition and Potentiation of A4\u03b22 Nicotinic Acetylcholine Receptors by Members of the Ly6 Protein Family","volume":"290","author":"Wu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.neures.2009.04.014","article-title":"Primary Sensory Neuronal Expression of SLURP-1, an Endogenous Nicotinic Acetylcholine Receptor Ligand","volume":"64","author":"Moriwaki","year":"2009","journal-title":"Neurosci. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/S0896-6273(02)00632-3","article-title":"Novel Modulation of Neuronal Nicotinic Acetylcholine Receptors by Association with the Endogenous Prototoxin Lynx1","volume":"33","author":"Miwa","year":"2002","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.neurobiolaging.2016.06.009","article-title":"Lynx1 and A\u03b21\u201342 Bind Competitively to Multiple Nicotinic Acetylcholine Receptor Subtypes","volume":"46","author":"Thomsen","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1134\/S1607672923700217","article-title":"Accumulation of \u03b2-Amyloid Leads to a Decrease in Lynx1 and Lypd6b Expression in the Hippocampus and Increased Expression of pro-Inflammatory Cytokines in the Hippocampus and Blood Serum","volume":"511","author":"Bychkov","year":"2023","journal-title":"Dokl. Biochem. Biophys."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00429-009-0227-3","article-title":"Presenilin Transgenic Mice as Models of Alzheimer\u2019s Disease","volume":"214","author":"Elder","year":"2010","journal-title":"Brain Struct. Funct."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1016\/j.neurobiolaging.2015.01.001","article-title":"Prostate Stem Cell Antigen Interacts with Nicotinic Acetylcholine Receptors and Is Affected in Alzheimer\u2019s Disease","volume":"36","author":"Jensen","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cai, W., Wu, T., and Chen, N. (2023). The Amyloid-Beta Clearance: From Molecular Targets to Glial and Neural Cells. Biomolecules, 13.","DOI":"10.3390\/biom13020313"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"110158","DOI":"10.1016\/j.celrep.2021.110158","article-title":"TREM2-Independent Oligodendrocyte, Astrocyte, and T Cell Responses to Tau and Amyloid Pathology in Mouse Models of Alzheimer Disease","volume":"37","author":"Lee","year":"2021","journal-title":"Cell Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"741","DOI":"10.3233\/JAD-2010-101020","article-title":"Amyloid-\u03b2 as a Modulator of Synaptic Plasticity","volume":"22","author":"Parihar","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1073\/pnas.95.4.1735","article-title":"Prostate Stem Cell Antigen: A Cell Surface Marker Overexpressed in Prostate Cancer","volume":"95","author":"Reiter","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10618","DOI":"10.1074\/jbc.M110.189100","article-title":"NMR Structure and Action on Nicotinic Acetylcholine Receptors of Water-Soluble Domain of Human LYNX1","volume":"286","author":"Lyukmanova","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/jnc.12728","article-title":"Impairments of Long-Term Depression Induction and Motor Coordination Precede A\u03b2 Accumulation in the Cerebellum of APPswe\/PS1dE9 Double Transgenic Mice","volume":"130","author":"Kuwabara","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1038\/sj.bjp.0707264","article-title":"The Alpha7 Nicotinic Acetylcholine Receptor as a Pharmacological Target for Inflammation","volume":"151","author":"Ulloa","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.2353\/ajpath.2009.090212","article-title":"{alpha}7 Nicotinic Acetylcholine Receptor Regulates Airway Epithelium Differentiation by Controlling Basal Cell Proliferation","volume":"175","author":"Maouche","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"325","DOI":"10.3389\/fncel.2018.00325","article-title":"The Role of KLF4 in Alzheimer\u2019s Disease","volume":"12","author":"Cheng","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8433","DOI":"10.1167\/iovs.12-10759","article-title":"Klf4 Regulates the Expression of Slurp1, Which Functions as an Immunomodulatory Peptide in the Mouse Cornea","volume":"53","author":"Swamynathan","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1167\/iovs.08-1811","article-title":"Identification of Candidate Klf4 Target Genes Reveals the Molecular Basis of the Diverse Regulatory Roles of Klf4 in the Mouse Cornea","volume":"49","author":"Swamynathan","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1007\/s00702-016-1580-z","article-title":"Astrocytic and Microglial Nicotinic Acetylcholine Receptors: An Overlooked Issue in Alzheimer\u2019s Disease","volume":"123","author":"Majdi","year":"2016","journal-title":"J. Neural. Transm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3389\/fnmol.2017.00427","article-title":"Involvement of Astrocytes in Alzheimer\u2019s Disease from a Neuroinflammatory and Oxidative Stress Perspective","volume":"10","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.tins.2021.07.006","article-title":"Astrocytic Processes: From Tripartite Synapses to the Active Milieu","volume":"44","author":"Semyanov","year":"2021","journal-title":"Trends Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/bs.acc.2020.02.002","article-title":"Advances in Biomarker Development in Acetaminophen Toxicity","volume":"98","author":"James","year":"2020","journal-title":"Adv. Clin. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"371","DOI":"10.4329\/wjr.v9.i10.371","article-title":"Cerebellum and Neurodegenerative Diseases: Beyond Conventional Magnetic Resonance Imaging","volume":"9","author":"Mormina","year":"2017","journal-title":"World J. Radiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1172\/JCI66407","article-title":"Familial Alzheimer\u2019s Disease-Associated Presenilin-1 Alters Cerebellar Activity and Calcium Homeostasis","volume":"124","author":"Hagel","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"396","DOI":"10.3389\/fnagi.2018.00396","article-title":"The Emerging Role of Altered Cerebellar Synaptic Processing in Alzheimer\u2019s Disease","volume":"10","author":"Hoxha","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1515\/revneuro-2019-0089","article-title":"Amyloid-\u03b2, Tau, and the Cholinergic System in Alzheimer\u2019s Disease: Seeking Direction in a Tangle of Clues","volume":"31","author":"Majdi","year":"2020","journal-title":"Rev. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chen, Z.-R., Huang, J.-B., Yang, S.-L., and Hong, F.-F. (2022). Role of Cholinergic Signaling in Alzheimer\u2019s Disease. Molecules, 27.","DOI":"10.3390\/molecules27061816"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1096\/fj.15-274548","article-title":"The Prototoxin LYPD6B Modulates Heteromeric A3\u03b24-Containing Nicotinic Acetylcholine Receptors, but Not A7 Homomers","volume":"30","author":"Ochoa","year":"2016","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13041-014-0075-9","article-title":"Cortical Parvalbumin and Somatostatin GABA Neurons Express Distinct Endogenous Modulators of Nicotinic Acetylcholine Receptors","volume":"7","author":"Demars","year":"2014","journal-title":"Mol. Brain"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"703748","DOI":"10.3389\/fnbeh.2021.703748","article-title":"Differential Expression Patterns of Lynx Proteins and Involvement of Lynx1 in Prepulse Inhibition","volume":"15","author":"Sherafat","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.euroneuro.2009.03.007","article-title":"Modulation of the Ca2+ Conductance of Nicotinic Acetylcholine Receptors by Lypd6","volume":"19","author":"Darvas","year":"2009","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1007\/s00429-013-0611-x","article-title":"Expression of the Ly-6 Family Proteins Lynx1 and Ly6H in the Rat Brain Is Compartmentalized, Cell-Type Specific, and Developmentally Regulated","volume":"219","author":"Thomsen","year":"2014","journal-title":"Brain Struct. Funct."},{"key":"ref_56","first-page":"321","article-title":"C-Jun N-Terminal Kinase (JNK) Signaling as a Therapeutic Target for Alzheimer\u2019s Disease","volume":"6","author":"Yarza","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s12031-012-9837-y","article-title":"Inhibition of Phosphorylation of JNK Suppresses A\u03b2-Induced ER Stress and Upregulates Prosurvival Mitochondrial Proteins in Rat Hippocampus","volume":"49","author":"Yenki","year":"2013","journal-title":"J. Mol. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"57","DOI":"10.32607\/20758251-2018-10-3-57-61","article-title":"Lynx1 Prevents Long-Term Potentiation Blockade and Reduction of Neuromodulator Expression Caused by A\u03b21-42 and JNK Activation","volume":"10","author":"Bychkov","year":"2018","journal-title":"Acta Naturae"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.neuron.2006.07.025","article-title":"The Prototoxin Lynx1 Acts on Nicotinic Acetylcholine Receptors to Balance Neuronal Activity and Survival in Vivo","volume":"51","author":"Miwa","year":"2006","journal-title":"Neuron"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"619626","DOI":"10.3389\/fneur.2021.619626","article-title":"The Many Faces of Astrocytes in Alzheimer\u2019s Disease","volume":"12","author":"Monterey","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_61","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_62","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","article-title":"Inflammation as a Central Mechanism in Alzheimer\u2019s Disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1134\/S1068162019020122","article-title":"Human Nicotinic Acetylcholine Receptors: Part II. Non-Neuronal Cholinergic System","volume":"45","author":"Shulepko","year":"2019","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.gene.2017.02.025","article-title":"Kr\u00fcppel-like Factor 4 (KLF4): What We Currently Know","volume":"611","author":"Ghaleb","year":"2017","journal-title":"Gene"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.nurt.2010.05.017","article-title":"Astrocytes in Alzheimer\u2019s Disease","volume":"7","author":"Verkhratsky","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.neuroscience.2015.01.007","article-title":"Astrocytes in Physiological Aging and Alzheimer\u2019s Disease","volume":"323","author":"Parpura","year":"2016","journal-title":"Neuroscience"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/glia.20967","article-title":"Concomitant Astroglial Atrophy and Astrogliosis in a Triple Transgenic Animal Model of Alzheimer\u2019s Disease","volume":"58","author":"Olabarria","year":"2010","journal-title":"Glia"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Preman, P., Alfonso-Triguero, M., Alberdi, E., Verkhratsky, A., and Arranz, A.M. (2021). Astrocytes in Alzheimer\u2019s Disease: Pathological Significance and Molecular Pathways. Cells, 10.","DOI":"10.20944\/preprints202102.0230.v1"},{"key":"ref_69","first-page":"531","article-title":"Surface Complexity of Human Neocortical Astrocytic Cells: Changes with Development, Aging, and Dementia","volume":"36","author":"Senitz","year":"1995","journal-title":"J. Hirnforsch."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1146\/annurev-neuro-070918-050443","article-title":"The Emerging Nature of Astrocyte Diversity","volume":"42","author":"Khakh","year":"2019","journal-title":"Annu. Rev. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14852\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:04:25Z","timestamp":1760130265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14852"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,3]]},"references-count":70,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms241914852"],"URL":"https:\/\/doi.org\/10.3390\/ijms241914852","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,3]]}}}