{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:37:20Z","timestamp":1789677440826,"version":"4.0.1"},"reference-count":143,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\n                    Alzheimer\u2019s disease (AD) begins decades before clinical symptoms emerge. The \u201camyloid hypothesis\u201d suggests that amyloid-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (A\u03b2) deposition initiates a cascade of tau hyperphosphorylation, neuroinflammation, and neuronal loss leading to cognitive decline. The recent success of anti-A\u03b2 therapies such as Leqembi in prodromal or mild cognitive impaired patients underscores the importance of early intervention and A\u03b2 clearance. However, safety and cost limitations highlight the need for alternative therapeutic strategies. Small-molecule modulators of Sigma-1 and Sigma-2 receptors (\u03c31R and \u03c32R) have emerged as promising candidates for AD treatment. \u03c31R agonists exhibit neuroprotective and anti-amnestic effects under pathological conditions without affecting normal cognition. Beyond AD, \u03c31R is implicated in several neurodegenerative diseases including ALS (amyotrophic lateral sclerosis), Parkinson\u2019s, and Huntington\u2019s diseases, stroke, and epilepsy. \u03c31R plays a key role at mitochondria-associated ER membranes (MAMs)\u2014specialized lipid raft-like domains that form functional membrane contact sites between the endoplasmic reticulum (ER) and mitochondria.\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -secretase (BACE1),\n                    <jats:italic>\u03b3<\/jats:italic>\n                    -secretase, and their substrates APP and palmitoylated APP (palAPP) localize in the MAMs, promoting amyloidogenic A\u03b2 production. MAMs serve as dynamic hubs for inter-organelle communication, calcium signaling, and lipid metabolism. The \u201cMAM hypothesis\u201d proposes that MAM dysregulation drives early AD pathology and persists throughout disease progression, contributing to neurofibrillary tangle formation, calcium imbalance, and neuroinflammation. This review aims to summarize the current understanding of \u03c31R-mediated regulation of MAMs and its neuroprotective mechanisms, highlighting potential therapeutic opportunities for targeting \u03c31R in AD and other neurodegenerative disorders.\n                  <\/jats:p>","DOI":"10.3389\/fnins.2025.1733659","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T12:30:38Z","timestamp":1766147438000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Sigma receptors and mitochondria-associated ER membranes are converging therapeutic targets for Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"19","author":[{"given":"Madhura S.","family":"Lotlikar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob C.","family":"Zellmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja","family":"Bhattacharyya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.jalz.2016.12.006","article-title":"Calcium hypothesis of Alzheimer's disease and brain aging: a framework for integrating new evidence into a comprehensive theory of pathogenesis","volume":"13","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.ejphar.2015.03.067","article-title":"Elements in support of the \u2018non-identity\u2019 of the PGRMC1 protein with the \u03c32 receptor","volume":"758","author":"Abate","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1016\/j.jsps.2022.10.004","article-title":"An update on the novel and approved drugs for Alzheimer disease","volume":"30","author":"Alhazmi","year":"2022","journal-title":"Saudi Pharm J"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1002\/ana.22534","article-title":"A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis","volume":"70","author":"Al-Saif","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.2353\/ajpath.2009.090219","article-title":"Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria","volume":"175","author":"Area-Gomez","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"4106","DOI":"10.1038\/emboj.2012.202","article-title":"Upregulated function of mitochondria-associated ER membranes in Alzheimer disease","volume":"31","author":"Area-Gomez","year":"2012","journal-title":"EMBO J."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1096\/fj.201601309","article-title":"On the pathogenesis of Alzheimer's disease: the MAM hypothesis","volume":"31","author":"Area-Gomez","year":"2017","journal-title":"FASEB J."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"176851","DOI":"10.1016\/j.ejphar.2024.176851","article-title":"Sigma-1 receptor modulation by clemastine highlights its repurposing as neuroprotective agent against seizures and cognitive deficits in PTZ-kindled rats","volume":"980","author":"Badawi","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2414827","DOI":"10.1002\/advs.202414827","article-title":"Development of carbon-11 labeled pyrimidine derivatives as novel positron emission tomography (PET) agents enabling brain sigma-1 receptor imaging","volume":"12","author":"Bai","year":"2025","journal-title":"Adv. Sci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e21954","DOI":"10.1371\/journal.pone.0021954","article-title":"Rivastigmine lowers a\u03b2 and increases sAPP\u03b1 levels, which parallel elevated synaptic markers and metabolic activity in degenerating primary rat neurons","volume":"6","author":"Bailey","year":"2011","journal-title":"PLoS One"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/wsbm.114","article-title":"Role of systems pharmacology in understanding drug adverse events","volume":"3","author":"Berger","year":"2011","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1093\/brain\/awv008","article-title":"Dysfunction in endoplasmic reticulum-mitochondria crosstalk underlies SIGMAR1 loss of function mediated motor neuron degeneration","volume":"138","author":"Bernard-Marissal","year":"2015","journal-title":"Brain"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"11169","DOI":"10.1523\/JNEUROSCI.4704-12.2013","article-title":"Palmitoylation of amyloid precursor protein regulates amyloidogenic processing in lipid rafts","volume":"33","author":"Bhattacharyya","year":"2013","journal-title":"J. Neurosci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"109134","DOI":"10.1016\/j.celrep.2021.109134","article-title":"Axonal generation of amyloid-beta from palmitoylated APP in mitochondria-associated endoplasmic reticulum membranes","volume":"35","author":"Bhattacharyya","year":"2021","journal-title":"Cell Rep."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1007\/s10571-018-0583-8","article-title":"The SERCA2: A gatekeeper of neuronal calcium homeostasis in the brain","volume":"38","author":"Britzolaki","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"197","DOI":"10.14283\/jpad.2022.30","article-title":"Two randomized phase 3 studies of aducanumab in early Alzheimer's disease","volume":"9","author":"Budd Haeberlein","year":"2022","journal-title":"J. Prev Alzheimers Dis."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.drudis.2016.11.005","article-title":"Doxorubicin: nanotechnological overviews from bench to bedside","volume":"22","author":"Cagel","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref18","doi-asserted-by":"publisher","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's disease","volume":"11","author":"Calvo-Rodriguez","year":"2020","journal-title":"Nat. Commun."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.3233\/JAD-180263","article-title":"Metformin use associated with reduced risk of dementia in patients with diabetes: A systematic review and Meta-analysis","volume":"65","author":"Campbell","year":"2018","journal-title":"J Alzheimer's Dis"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"108827","DOI":"10.1016\/j.celrep.2021.108827","article-title":"BOK controls apoptosis by ca(2+) transfer through ER-mitochondrial contact sites","volume":"34","author":"Carpio","year":"2021","journal-title":"Cell Rep."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e51954","DOI":"10.15252\/embr.202051954","article-title":"Mfn2 localization in the ER is necessary for its bioenergetic function and neuritic development","volume":"22","author":"Casellas-D\u00edaz","year":"2021","journal-title":"EMBO Rep."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"P1570","DOI":"10.1016\/j.jalz.2017.07.730","article-title":"[P4\u2013567]: A phase 1 safety trial of the a\u03b2 oligomer receptor antagonist CT1812","volume":"13","author":"Catalano","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/s41398-024-02755-9","article-title":"Reconsidering repurposing: long-term metformin treatment impairs cognition in Alzheimer\u2019s model mice","volume":"14","author":"Cho","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1016\/j.ebiom.2015.10.017","article-title":"The Sigma-2 receptor and progesterone receptor membrane component 1 are different binding sites derived from independent genes","volume":"2","author":"Chu","year":"2015","journal-title":"EBioMedicine"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e18565","DOI":"10.1111\/jcmm.18565","article-title":"Effect of tangeretin on cisplatin-induced oxido-inflammatory brain damage in rats","volume":"28","author":"Cicek","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1038\/s41418-017-0033-z","article-title":"SPLICS: a split green fluorescent protein-based contact site sensor for narrow and wide heterotypic organelle juxtaposition","volume":"25","author":"Cieri","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1007\/s00401-023-02679-6","article-title":"Transmembrane protein 97 is a potential synaptic amyloid beta receptor in human Alzheimer\u2019s disease","volume":"147","author":"Colom-Cadena","year":"2024","journal-title":"Acta Neuropathol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"106740","DOI":"10.1016\/j.nbd.2024.106740","article-title":"Mitochondrial plasticity: an emergent concept in neuronal plasticity and memory","volume":"203","author":"Comyn","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.euroneuro.2020.08.010","article-title":"Sigma-1 (sigma(1)) receptor activity is necessary for physiological brain plasticity in mice","volume":"39","author":"Crouzier","year":"2020","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1083\/jcb.200604016","article-title":"Structural and functional features and significance of the physical linkage between ER and mitochondria","volume":"174","author":"Csordas","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"102713","DOI":"10.1016\/j.arr.2025.102713","article-title":"Mitochondrial dysfunction in Alzheimer\u2019s disease","volume":"107","author":"D\u2019Alessandro","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/S0006-8993(02)03152-9","article-title":"Impaired axonal transport of cortical neurons in Alzheimer\u2019s disease is associated with neuropathological changes","volume":"948","author":"Dai","year":"2002","journal-title":"Brain Res."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e70614","DOI":"10.1002\/alz.70614","article-title":"Enhancing uptake of antidiabetic drugs to reduce cardiometabolic risk and dementia burden","volume":"21","author":"Daly","year":"2025","journal-title":"Alzheimers Dement."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/nature07534","article-title":"Mitofusin 2 tethers endoplasmic reticulum to mitochondria","volume":"456","author":"de Brito","year":"2008","journal-title":"Nature"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1093\/hmg\/ddr559","article-title":"VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis","volume":"21","author":"De Vos","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1038\/s42003-024-06933-9","article-title":"ER-mitochondria distance is a critical parameter for efficient mitochondrial Ca2+ uptake and oxidative metabolism","volume":"7","author":"Dematteis","year":"2024","journal-title":"Commun. Biol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.3390\/biomedicines13061409","article-title":"Pharmacological and pathological implications of Sigma-1 receptor in neurodegenerative diseases","volume":"13","author":"Drewes","year":"2025","journal-title":"Biomedicine"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.chembiol.2013.03.004","article-title":"Structural systems pharmacology: the role of 3D structures in next-generation drug development","volume":"20","author":"Duran-Frigola","year":"2013","journal-title":"Chem. Biol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.neuint.2017.03.021","article-title":"From dysfunctional endoplasmic reticulum-mitochondria coupling to neurodegeneration","volume":"109","author":"Erpapazoglou","year":"2017","journal-title":"Neurochem. Int."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"7926","DOI":"10.1021\/acs.jmedchem.0c02265","article-title":"Recent advances in the development of sigma receptor ligands as cytotoxic agents: A medicinal chemistry perspective","volume":"64","author":"Fallica","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.neulet.2012.04.046","article-title":"Association between a variant of the sigma-1 receptor gene and Alzheimer's disease","volume":"517","author":"Feher","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3389\/fncel.2015.00191","article-title":"Soluble amyloid-b oligomers as synaptotoxins leading to cognitive impairment in Alzheimer\u2019s disease","volume":"9","author":"Ferreira","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"E2174","DOI":"10.1073\/pnas.1504880112","article-title":"Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling","volume":"112","author":"Filadi","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.cmet.2014.09.018","article-title":"Metformin: from mechanisms of action to therapies","volume":"20","author":"Foretz","year":"2014","journal-title":"Cell Metab."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/B978-0-12-386033-0.00002-5","article-title":"New insights into the role of mitochondria-associated endoplasmic reticulum membrane","volume":"292","author":"Fujimoto","year":"2011","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1038\/cdd.2016.52","article-title":"The coming of age of the mitochondria-ER contact: a matter of thickness","volume":"23","author":"Giacomello","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s40478-019-0688-4","article-title":"The VAPB-PTPIP51 endoplasmic reticulum-mitochondria tethering proteins are present in neuronal synapses and regulate synaptic activity","volume":"7","author":"G\u00f3mez-Suaga","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"102161","DOI":"10.1016\/j.arr.2023.102161","article-title":"Once upon a time, the amyloid Cascade hypothesis","volume":"93","author":"Granzotto","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1083\/jcb.200706171","article-title":"SERCA pump activity is physiologically regulated by presenilin and regulates amyloid beta production","volume":"181","author":"Green","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"3741","DOI":"10.1093\/hmg\/ddw220","article-title":"Loss-of-function mutations in the SIGMAR1 gene cause distal hereditary motor neuropathy by impairing ER-mitochondria tethering and Ca2+ signalling","volume":"25","author":"Gregianin","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.trci.2018.11.001","article-title":"A phase 1 clinical trial of the sigma-2 receptor complex allosteric antagonist CT1812, a novel therapeutic candidate for Alzheimer's disease","volume":"5","author":"Grundman","year":"2019","journal-title":"Alzheimer's & Dementia: Translational Res. Clin. Interventions"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"107409","DOI":"10.1016\/j.phrs.2024.107409","article-title":"A new perspective on liver diseases: focusing on the mitochondria-associated endoplasmic reticulum membranes","volume":"208","author":"Guo","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"24069","DOI":"10.1038\/s41598-021-03406-5","article-title":"Association of metformin use with Alzheimer's disease in patients with newly diagnosed type 2 diabetes: a population-based nested case-control study","volume":"11","author":"Ha","year":"2021","journal-title":"Sci. Rep."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","article-title":"The amyloid-beta pathway in Alzheimer's disease","volume":"26","author":"Hampel","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"e12013","DOI":"10.1002\/trc2.12013","article-title":"A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer's disease therapy: analysis of the blarcamesine (ANAVEX2-73) phase 2a clinical study","volume":"6","author":"Hampel","year":"2020","journal-title":"Alzheimers Dement (NY)"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/nrg4017","article-title":"Protective alleles and modifier variants in human health and disease","volume":"16","author":"Harper","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"733","DOI":"10.3389\/fnins.2019.00733","article-title":"The Sigma-1 receptor in cellular stress signaling","volume":"13","author":"Hayashi","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.cell.2007.08.036","article-title":"Sigma-1 receptor chaperones at the ER- mitochondrion Interface regulate Ca2+ signaling and cell survival","volume":"131","author":"Hayashi","year":"2007","journal-title":"Cell"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/0006-8993(90)91143-5","article-title":"A sigma-like binding site in rat pheochromocytoma (PC12) cells: decreased affinity for (+)-benzomorphans and lower molecular weight suggest a different sigma receptor form from that of guinea pig brain","volume":"527","author":"Hellewell","year":"1990","journal-title":"Brain Res."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1241638","DOI":"10.3389\/fneur.2023.1241638","article-title":"Clinical, imaging, and biomarker evidence of amyloid- and tau-related neurodegeneration in late-onset epilepsy of unknown etiology","volume":"14","author":"Hickman","year":"2023","journal-title":"Front. Neurol."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1126\/science.aan6009","article-title":"ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons","volume":"358","author":"Hirabayashi","year":"2017","journal-title":"Science"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"765","DOI":"10.2174\/156720511797633232","article-title":"Genetic polymorphisms in sigma-1 receptor and apolipoprotein E interact to influence the severity of Alzheimer's disease","volume":"8","author":"Huang","year":"2011","journal-title":"Curr. Alzheimer Res."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"e111899","DOI":"10.1371\/journal.pone.0111899","article-title":"Alzheimer's therapeutics targeting amyloid beta 1\u201342 oligomers II: sigma-2\/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity","volume":"9","author":"Izzo","year":"2014","journal-title":"PLoS One"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/0006-8993(93)91441-t","article-title":"Loss of sigma binding sites in the CA1 area of the anterior hippocampus in Alzheimer's disease correlates with CA1 pyramidal cell loss","volume":"623","author":"Jansen","year":"1993","journal-title":"Brain Res."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"20406223221109454","DOI":"10.1177\/20406223221109454","article-title":"Metformin and the risk of dementia based on an analysis of 396,332 participants","volume":"13","author":"Ji","year":"2022","journal-title":"Ther Adv Chronic Dis"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"2852","DOI":"10.1021\/acschemneuro.2c00274","article-title":"Neuroprotective effects of \u03c3(2)R\/TMEM97 receptor modulators in the neuronal model of Huntington's disease","volume":"13","author":"Jin","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref67","first-page":"4808","article-title":"Roles of sigma-1 receptors in Alzheimer's disease","volume":"8","author":"Jin","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"6779","DOI":"10.1038\/s41467-022-34365-8","article-title":"Capture at the ER-mitochondrial contacts licenses IP(3) receptors to stimulate local ca(2+) transfer and oxidative metabolism","volume":"13","author":"Katona","year":"2022","journal-title":"Nat. Commun."},{"key":"ref69","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241612980","article-title":"Structure-based modeling of sigma 1 receptor interactions with ligands and cholesterol and implications for its biological function","volume":"24","author":"Kim","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref70","doi-asserted-by":"crossref","DOI":"10.1007\/164_2017_38","article-title":"Sigma1 pharmacology in the context of Cancer","volume-title":"Sigma proteins: Evolution of the concept of sigma receptors","author":"Kim","year":"2017"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"13176","DOI":"10.1096\/fj.201901136R","article-title":"Mitochondrial morphology regulates organellar Ca2+ uptake and changes cellular Ca2+ homeostasis","volume":"33","author":"Kowaltowski","year":"2019","journal-title":"FASEB J."},{"key":"ref72","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122552","article-title":"Amyloid beta-peptide increases mitochondria-endoplasmic reticulum contact altering mitochondrial function and autophagosome formation in Alzheimer's disease-related models","volume":"9","author":"Leal","year":"2020","journal-title":"Cells"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1111\/jcmm.12863","article-title":"Mitofusin-2 knockdown increases ER-mitochondria contact and decreases amyloid beta-peptide production","volume":"20","author":"Leal","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1007\/s12035-012-8307-4","article-title":"From mitochondrial dysfunction to amyloid beta formation: novel insights into the pathogenesis of Alzheimer's disease","volume":"46","author":"Leuner","year":"2012","journal-title":"Mol. Neurobiol."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41540-021-00185-7","article-title":"Systems modeling predicts that mitochondria ER contact sites regulate the postsynaptic energy landscape","volume":"7","author":"Leung","year":"2021","journal-title":"NPJ Syst Biol Appl"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"10846","DOI":"10.3390\/ijms231810846","article-title":"Differential responses to Sigma-1 or Sigma-2 receptor ablation in adiposity, fat oxidation, and sexual dimorphism","volume":"23","author":"Li","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1002\/ana.22274","article-title":"Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration-motor neuron disease","volume":"68","author":"Luty","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1038\/nn.3486","article-title":"Suppression of eIF2\u03b1 kinases alleviates Alzheimer's disease-related plasticity and memory deficits","volume":"16","author":"Ma","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"100016","DOI":"10.1016\/j.tjpad.2024.100016","article-title":"Blarcamesine for the treatment of early Alzheimer's disease: results from the ANAVEX2-73-AD-004 phase IIB\/III trial","volume":"12","author":"Macfarlane","year":"2025","journal-title":"J. Prev Alzheimers Dis."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.3390\/cells9071637","article-title":"Chemical modulation of mitochondria-endoplasmic reticulum contact sites","volume":"9","author":"Magalhaes Rebelo","year":"2020","journal-title":"Cells"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1007\/s40263-023-01007-6","article-title":"Targeting sigma receptors for the treatment of neurodegenerative and neurodevelopmental disorders","volume":"37","author":"Malar","year":"2023","journal-title":"CNS Drugs"},{"key":"ref82","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.229906","article-title":"Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease","volume":"132","author":"Martino Adami","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1159\/000101990","article-title":"Sigma receptor type 1 gene variation in a group of polish patients with Alzheimer's disease and mild cognitive impairment","volume":"23","author":"Maruszak","year":"2007","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/164_2017_15","article-title":"Sigma-1 (sigma(1)) receptor in memory and neurodegenerative diseases","volume":"244","author":"Maurice","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.pharmthera.2009.07.001","article-title":"The pharmacology of sigma-1 receptors","volume":"124","author":"Maurice","year":"2009","journal-title":"Pharmacol. Ther."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1016\/j.ejca.2009.07.011","article-title":"Screening of anti-glioma effects induced by sigma-1 receptor ligands: potential new use for old anti-psychiatric medicines","volume":"45","author":"Megalizzi","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1593\/neo.07130","article-title":"4-IBP, a sigma1 receptor agonist, decreases the migration of human cancer cells, including glioblastoma cells, in vitro and sensitizes them in vitro and in vivo to cytotoxic insults of proapoptotic and proautophagic drugs","volume":"9","author":"Megalizzi","year":"2007","journal-title":"Neoplasia"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/978-3-319-50174-1_8","article-title":"Pharmacological modulation of the sigma 1 receptor and the treatment of pain","volume":"964","author":"Merlos","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"4145","DOI":"10.1523\/JNEUROSCI.6338-11.2012","article-title":"Mitofusin2 mutations disrupt axonal mitochondrial positioning and promote axon degeneration","volume":"32","author":"Misko","year":"2012","journal-title":"J. Neurosci."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"419","DOI":"10.3389\/fphar.2019.00419","article-title":"Molecular interplay between the Sigma-1 receptor, steroids, and ion channels","volume":"10","author":"Morales-L\u00e1zaro","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12858-015-0040-y","article-title":"Sigma-1 receptor directly interacts with Rac1-GTPase in the brain mitochondria","volume":"16","author":"Natsvlishvili","year":"2015","journal-title":"BMC Biochem."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.neuron.2019.12.007","article-title":"TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge","volume":"105","author":"Nugent","year":"2020","journal-title":"Neuron"},{"key":"ref93","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abc5429","article-title":"Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer's disease","volume":"14","author":"Oliveira","year":"2021","journal-title":"Sci. Signal."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1158\/2767-9764.CRC-22-0371","article-title":"Sigma1 regulates lipid droplet-mediated redox homeostasis required for prostate Cancer proliferation","volume":"3","author":"Oyer","year":"2023","journal-title":"Cancer Res Commun"},{"key":"ref95","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00048","article-title":"Axonal endoplasmic reticulum dynamics and its roles in neurodegeneration","volume":"14","author":"\u00d6zt\u00fcrk","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"e2217864120","DOI":"10.1073\/pnas.2217864120","article-title":"A Cdk5-derived peptide inhibits Cdk5\/p25 activity and improves neurodegenerative phenotypes","volume":"120","author":"Pao","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"3356","DOI":"10.15252\/embj.201796797","article-title":"Increased localization of APP-C99 in mitochondria-associated ER membranes causes mitochondrial dysfunction in Alzheimer disease","volume":"36","author":"Pera","year":"2017","journal-title":"EMBO J."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1007\/s43440-021-00310-7","article-title":"Sigma receptors and neurological disorders","volume":"73","author":"Piechal","year":"2021","journal-title":"Pharmacol. Rep."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"753","DOI":"10.3892\/ijo.2016.3558","article-title":"Influence of doxorubicin on apoptosis and oxidative stress in breast cancer cell lines","volume":"49","author":"Pilco-Ferreto","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41580-019-0180-9","article-title":"The functional universe of membrane contact sites","volume":"21","author":"Prinz","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.molcel.2015.08.001","article-title":"MAPL SUMOylation of Drp1 stabilizes an ER\/mitochondrial platform required for cell death","volume":"59","author":"Prudent","year":"2015","journal-title":"Mol. Cell"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41398-020-0709-x","article-title":"Rivastigmine modifies the \u03b1-secretase pathway and potentially early Alzheimer's disease","volume":"10","author":"Ray","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"16845","DOI":"10.1038\/s41598-018-35430-3","article-title":"Sigma-2 receptor\/TMEM97 and PGRMC-1 increase the rate of internalization of LDL by LDL receptor through the formation of a ternary complex","volume":"8","author":"Riad","year":"2018","journal-title":"Sci. Rep."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1038\/s42003-023-05511-9","article-title":"Synaptic proteasome is inhibited in Alzheimer's disease models and associates with memory impairment in mice","volume":"6","author":"Ribeiro","year":"2023","journal-title":"Commun Biol"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1021\/acsmedchemlett.1c00048","article-title":"Discovery of investigational drug CT1812, an antagonist of the Sigma-2 receptor complex for Alzheimer\u2019s disease","volume":"12","author":"Rishton","year":"2021","journal-title":"ACS Med. Chem. Lett."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1126\/science.aao1785","article-title":"MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-tooth disease type 2A","volume":"360","author":"Rocha","year":"2018","journal-title":"Science"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.jalz.2012.01.002","article-title":"Effectiveness of antidementia drugs in delaying Alzheimer's disease progression","volume":"9","author":"Rountree","year":"2013","journal-title":"Alzheimers Dement."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1007\/s11481-024-10144-8","article-title":"Sigma-1 receptors control neuropathic pain and peripheral Neuroinflammation after nerve injury in female mice: A transcriptomic study","volume":"19","author":"Ruiz-Cantero","year":"2024","journal-title":"J. NeuroImmune Pharmacol."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"105339","DOI":"10.1016\/j.phrs.2020.105339","article-title":"Sigma-1 receptor: A drug target for the modulation of neuroimmune and neuroglial interactions during chronic pain","volume":"163","author":"Ruiz-Cantero","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1016\/j.neubiorev.2021.10.037","article-title":"Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders","volume":"132","author":"Sa\u0142aciak","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s13041-020-00676-4","article-title":"The sigma 2 receptor promotes and the sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception","volume":"13","author":"S\u00e1nchez-Bl\u00e1zquez","year":"2020","journal-title":"Mol. Brain"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1007\/s00125-017-4336-x","article-title":"Metformin: clinical use in type 2 diabetes","volume":"60","author":"Sanchez-Rangel","year":"2017","journal-title":"Diabetologia"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.tips.2019.07.006","article-title":"The molecular function of \u03c3 receptors: past, present, and future","volume":"40","author":"Schmidt","year":"2019","journal-title":"Trends Pharmacol. Sci."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/nature17391","article-title":"Crystal structure of the human \u03c31 receptor","volume":"532","author":"Schmidt","year":"2016","journal-title":"Nature"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.mcn.2012.07.011","article-title":"Mitochondria-associated ER membranes in Alzheimer disease","volume":"55","author":"Schon","year":"2013","journal-title":"Mol. Cell. Neurosci."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"14484","DOI":"10.1523\/JNEUROSCI.2567-14.2014","article-title":"Inhibiting ACAT1\/SOAT1 in microglia stimulates autophagy-mediated lysosomal proteolysis and increases Abeta1-42 clearance","volume":"34","author":"Shibuya","year":"2014","journal-title":"J. Neurosci."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.1016\/j.neurobiolaging.2015.04.002","article-title":"Acyl-coenzyme A:cholesterol acyltransferase 1 blockage enhances autophagy in the neurons of triple transgenic Alzheimer's disease mouse and reduces human P301L-tau content at the presymptomatic stage","volume":"36","author":"Shibuya","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/B978-0-12-394816-8.00003-9","article-title":"Mitochondrial abnormalities in Alzheimer's disease: possible targets for therapeutic intervention","volume":"64","author":"Silva","year":"2012","journal-title":"Adv. Pharmacol."},{"key":"ref119","doi-asserted-by":"publisher","DOI":"10.3390\/cells8010005","article-title":"Perspective: mitochondria-ER contacts in metabolic cellular stress assessed by microscopy","volume":"8","author":"Stacchiotti","year":"2018","journal-title":"Cells"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.tips.2010.08.007","article-title":"The sigma-1 receptor chaperone as an inter-organelle signaling modulator","volume":"31","author":"Su","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.molcel.2013.04.023","article-title":"MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2","volume":"51","author":"Sugiura","year":"2013","journal-title":"Mol. Cell"},{"key":"ref122","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1134\/S0026893322010071","article-title":"Molecular mechanisms of interactions between mitochondria and the endoplasmic reticulum: A new Look at how important cell functions are supported","volume":"56","author":"Sukhorukov","year":"2022","journal-title":"Mol. Biol."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.biocel.2017.05.006","article-title":"Doxorubicin-induced cardiomyocyte apoptosis: role of mitofusin 2","volume":"88","author":"Tang","year":"2017","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref124","doi-asserted-by":"publisher","first-page":"e0209250","DOI":"10.1371\/journal.pone.0209250","article-title":"Cholinesterase inhibitor rivastigmine enhances nerve growth factor-induced neurite outgrowth in PC12 cells via sigma-1 and sigma-2 receptors","volume":"13","author":"Terada","year":"2018","journal-title":"PLoS One"},{"key":"ref125","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1089\/ars.2005.7.1101","article-title":"Differentiated Alzheimer's disease transmitochondrial cybrid cell lines exhibit reduced organelle movement","volume":"7","author":"Trimmer","year":"2005","journal-title":"Antioxid. Redox Signal."},{"key":"ref126","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1038\/sj.onc.1208313","article-title":"Inositol 1,4,5-trisphosphate (IP3) receptor type1 (IP3R1) modulates the acquisition of cisplatin resistance in bladder cancer cell lines","volume":"24","author":"Tsunoda","year":"2005","journal-title":"Oncogene"},{"key":"ref127","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1111\/j.1365-2443.2005.00827.x","article-title":"Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease","volume":"10","author":"Uchida","year":"2005","journal-title":"Genes Cells"},{"key":"ref128","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer's disease","volume":"388","author":"van Dyck","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref129","doi-asserted-by":"publisher","first-page":"eabk1051","DOI":"10.1126\/scitranslmed.abk1051","article-title":"Widespread cell stress and mitochondrial dysfunction occur in patients with early Alzheimer\u2019s disease","volume":"14","author":"Venkataraman","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref130","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.cell.2023.11.040","article-title":"Making the connection: how membrane contact sites have changed our view of organelle biology","volume":"187","author":"Voeltz","year":"2024","journal-title":"Cell"},{"key":"ref131","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512025","article-title":"The sigma receptors in Alzheimer's disease: new potential targets for diagnosis and therapy","volume":"24","author":"Wang","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref132","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s12974-024-03072-0","article-title":"Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson\u2019s disease through Mfn2-cGAS signaling","volume":"21","author":"Wang","year":"2024","journal-title":"J. Neuroinflammation"},{"key":"ref133","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.15252\/emmm.201606403","article-title":"Mitochondria-associated membrane collapse is a common pathomechanism in SIGMAR1- and SOD1-linked ALS","volume":"8","author":"Watanabe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref134","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/164_2017_33","article-title":"Medicinal chemistry of \u03c3(1) receptor ligands: pharmacophore models, synthesis, structure affinity relationships, and pharmacological applications","volume":"244","author":"Weber","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref135","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s12929-017-0380-6","article-title":"Roles of sigma-1 receptors on mitochondrial functions relevant to neurodegenerative diseases","volume":"24","author":"Weng","year":"2017","journal-title":"J. Biomed. Sci."},{"key":"ref136","doi-asserted-by":"publisher","first-page":"e1225242024","DOI":"10.1523\/JNEUROSCI.1225-24.2024","article-title":"Altered protein Palmitoylation as disease mechanism in neurodegenerative disorders","volume":"44","author":"Wlodarczyk","year":"2024","journal-title":"J. Neurosci."},{"key":"ref137","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.3892\/ijo.2016.3733","article-title":"ABT737 reverses cisplatin resistance by regulating ER-mitochondria Ca2+ signal transduction in human ovarian cancer cells","volume":"49","author":"Xie","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref138","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1111\/jnc.13917","article-title":"Small molecule modulator of sigma 2 receptor is neuroprotective and reduces cognitive deficits and neuroinflammation in experimental models of Alzheimer's disease","volume":"140","author":"Yi","year":"2017","journal-title":"J. Neurochem."},{"key":"ref139","doi-asserted-by":"publisher","first-page":"e66129","DOI":"10.3791\/66129","article-title":"Quantitative analysis of mitochondria-associated endoplasmic reticulum membrane (MAM) stabilization in a neural model of Alzheimer's disease (AD)","author":"Zellmer","year":"2025","journal-title":"JoVE"},{"key":"ref140","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/alz.14417","article-title":"Stabilization of mitochondria-associated endoplasmic reticulum membranes regulates a\u03b2 generation in a three-dimensional neural model of Alzheimer's disease","author":"Zellmer","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref141","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092195","article-title":"Communications between mitochondria and endoplasmic reticulum in the regulation of metabolic homeostasis","volume":"10","author":"Zhang","year":"2021","journal-title":"Cells"},{"key":"ref142","doi-asserted-by":"publisher","DOI":"10.1172\/JCI147307","article-title":"Restoring mitofusin balance prevents axonal degeneration in a Charcot-Marie-tooth type 2A model","volume":"131","author":"Zhou","year":"2021","journal-title":"J. Clin. Invest."},{"key":"ref143","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1038\/s42003-021-02840-5","article-title":"Cellular senescence links mitochondria-ER contacts and aging","volume":"4","author":"Ziegler","year":"2021","journal-title":"Commun Biol"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2025.1733659\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T12:30:40Z","timestamp":1766147440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2025.1733659\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":143,"alternative-id":["10.3389\/fnins.2025.1733659"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2025.1733659","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,19]]},"article-number":"1733659"}}