{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T23:12:17Z","timestamp":1768864337846,"version":"3.49.0"},"reference-count":70,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Neurological Disorders and Stroke of the National Institutes of Health","award":["R01 NS098772"],"award-info":[{"award-number":["R01 NS098772"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hyperphosphorylated collapsin response mediator protein 2 (CRMP2) is elevated in the cerebral cortex of an APP-SAA knock-in mouse model of Alzheimer\u2019s disease and binds the adenine nucleotide translocase (ANT) in a phosphorylation-dependent manner. We propose that, in Alzheimer\u2019s disease (AD) mitochondria, dissociation of hyperphosphorylated CRMP2 from ANT promotes opening of the permeability transition pore (PTP). We showed that purified ANT, when reconstituted into giant liposomes, forms large calcium-dependent channels resembling the PTP, which are effectively blocked by recombinant, unphosphorylated CRMP2. In synaptic mitochondria isolated from the cortices of APP-SAA knock-in mice and control B6J hAbeta mice, we observed an increased susceptibility to permeability transition pore (PTP) induction in AD mitochondria, accompanied by reduced viability of cultured cortical neurons. Pre-treatment of AD mice with the CRMP2-binding small molecule (S)-lacosamide ((S)-LCM), which prevents CRMP2 hyperphosphorylation and restores its interaction with ANT, attenuated PTP induction and improved neuronal viability. Interestingly, direct application of (S)-LCM to isolated mitochondria failed to suppress PTP induction, indicating that its protective effect requires upstream cellular mechanisms. These findings support a phosphorylation-dependent role for CRMP2 in regulating PTP induction in AD mitochondria and highlight (S)-LCM as a promising therapeutic candidate for mitigating mitochondrial dysfunction and enhancing neuronal viability in AD.<\/jats:p>","DOI":"10.3390\/cells15020179","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:57:02Z","timestamp":1768816622000},"page":"179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Collapsin Response Mediator Protein 2 (CRMP2) Modulates Induction of the Mitochondrial Permeability Transition Pore in a Knock-In Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Tatiana","family":"Brustovetsky","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Molecular Biology, and Pharmacology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajesh","family":"Khanna","sequence":"additional","affiliation":[{"name":"Center for Advanced Pain Therapeutics and Research (CAPToR), College of Medicine University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Pharmacology & Therapeutics, and McKnight Brain Institute, College of Medicine University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6564-2560","authenticated-orcid":false,"given":"Nickolay","family":"Brustovetsky","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology, and Pharmacology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Herrup, K. (2021). How Not to Study a Disease: The Stroty of Alzheimer\u2019s, The MIT Press.","DOI":"10.7551\/mitpress\/12423.001.0001"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/376509a0","article-title":"Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33","volume":"376","author":"Goshima","year":"1995","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s12035-011-8166-4","article-title":"Collapsin response mediator protein-2: An emerging pathologic feature and therapeutic target for neurodisease indications","volume":"43","author":"Hensley","year":"2011","journal-title":"Mol. Neurobiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/JAD-160076","article-title":"Collapsin Response Mediator Protein-2 (CRMP2) is a Plausible Etiological Factor and Potential Therapeutic Target in Alzheimer\u2019s Disease: Comparison and Contrast with Microtubule-Associated Protein Tau","volume":"53","author":"Hensley","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"949","DOI":"10.3233\/JAD-200721","article-title":"Collapsin Response Mediator Proteins: Novel Targets for Alzheimer\u2019s Disease","volume":"77","author":"Quach","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1021\/acschemneuro.0c00307","article-title":"Druggability of CRMP2 for Neurodegenerative Diseases","volume":"11","author":"Khanna","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3233\/JAD-2006-9S335","article-title":"GSK-3 is essential in the pathogenesis of Alzheimer\u2019s disease","volume":"9","author":"Takashima","year":"2006","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"864","DOI":"10.2174\/156720512802455386","article-title":"Roles of glycogen synthase kinase 3 in Alzheimer\u2019s disease","volume":"9","author":"Cai","year":"2012","journal-title":"Curr. Alzheimer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bbapap.2003.11.019","article-title":"Cdk5, a therapeutic target for Alzheimer\u2019s disease?","volume":"1697","author":"Tsai","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.arcmed.2012.10.015","article-title":"Deregulated Cdk5 activity is involved in inducing Alzheimer\u2019s disease","volume":"43","author":"Shukla","year":"2012","journal-title":"Arch. Med. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1021\/bi992323h","article-title":"Neurofibrillary tangle-associated collapsin response mediator protein-2 (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522","volume":"39","author":"Gu","year":"2000","journal-title":"Biochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"50176","DOI":"10.1074\/jbc.C400412200","article-title":"GSK-3 phosphorylation of the Alzheimer epitope within collapsin response mediator proteins regulates axon elongation in primary neurons","volume":"279","author":"Cole","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/j.1471-4159.2007.04829.x","article-title":"Collapsin response mediator protein-2 hyperphosphorylation is an early event in Alzheimer\u2019s disease progression","volume":"103","author":"Cole","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"269","DOI":"10.2174\/156720509788486572","article-title":"Increased CRMP2 phosphorylation is observed in Alzheimer\u2019s disease; does this tell us anything about disease development?","volume":"6","author":"Soutar","year":"2009","journal-title":"Curr. Alzheimer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.4103\/1673-5374.233451","article-title":"Amyloid-beta-dependent phosphorylation of collapsin response mediator protein-2 dissociates kinesin in Alzheimer\u2019s disease","volume":"13","author":"Mokhtar","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1093\/brain\/awm260","article-title":"The beta-amyloid protein of Alzheimer\u2019s disease increases neuronal CRMP-2 phosphorylation by a Rho-GTP mechanism","volume":"131","author":"Petratos","year":"2008","journal-title":"Brain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1021\/bi702030w","article-title":"Novel procedure to investigate the effect of phosphorylation on protein complex formation in vitro and in cells","volume":"47","author":"Rembutsu","year":"2008","journal-title":"Biochemistry"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Brustovetsky, T., Khanna, R., and Brustovetsky, N. (2021). CRMP2 Is Involved in Regulation of Mitochondrial Morphology and Motility in Neurons. Cells, 10.","DOI":"10.3390\/cells10102781"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1016\/j.bbamem.2008.04.011","article-title":"The ADP and ATP transport in mitochondria and its carrier","volume":"1778","author":"Klingenberg","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Brustovetsky, T., Khanna, R., and Brustovetsky, N. (2025). Collapsin Response Mediator Protein 2 (CRMP2) Modulates Mitochondrial Oxidative Metabolism in Knock-In AD Mouse Model. Cells, 14.","DOI":"10.20944\/preprints202503.2263.v1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1152\/physrev.1999.79.4.1127","article-title":"Mitochondrial transport of cations: Channels, exchangers, and permeability transition","volume":"79","author":"Bernardi","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bonora, M., Patergnani, S., Ramaccini, D., Morciano, G., Pedriali, G., Kahsay, A.E., Bouhamida, E., Giorgi, C., Wieckowski, M.R., and Pinton, P. (2020). Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology. Biomolecules, 10.","DOI":"10.3390\/biom10070998"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102719","DOI":"10.1016\/j.ceca.2023.102719","article-title":"The mitochondrial permeability transition pore in Ca2+ homeostasis","volume":"111","author":"Carraro","year":"2023","journal-title":"Cell Calcium"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18670","DOI":"10.1073\/pnas.1006586107","article-title":"Early deficits in synaptic mitochondria in an Alzheimer\u2019s disease mouse model","volume":"107","author":"Du","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jia, K., and Du, H. (2021). Mitochondrial Permeability Transition: A Pore Intertwines Brain Aging and Alzheimer\u2019s Disease. Cells, 10.","DOI":"10.3390\/cells10030649"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1093\/brain\/awad432","article-title":"New cyclophilin D inhibitor rescues mitochondrial and cognitive function in Alzheimer\u2019s disease","volume":"147","author":"Samanta","year":"2023","journal-title":"Brain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11483","DOI":"10.1038\/ncomms11483","article-title":"Deregulation of mitochondrial F1FO-ATP synthase via OSCP in Alzheimer\u2019s disease","volume":"7","author":"Beck","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.nbd.2018.09.020","article-title":"Cyclophilin D deficiency attenuates mitochondrial F1Fo ATP synthase dysfunction via OSCP in Alzheimer\u2019s disease","volume":"121","author":"Gauba","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/nm.1868","article-title":"Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer\u2019s disease","volume":"14","author":"Du","year":"2008","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.neurobiolaging.2009.03.003","article-title":"Cyclophilin D deficiency improves mitochondrial function and learning\/memory in aging Alzheimer disease mouse model","volume":"32","author":"Du","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1042\/bj3360287","article-title":"Direct demonstration of a specific interaction between cyclophilin-D and the adenine nucleotide translocase confirms their role in the mitochondrial permeability transition","volume":"336","author":"Woodfield","year":"1998","journal-title":"Biochem. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8483","DOI":"10.1021\/bi960833v","article-title":"Mitochondrial ADP\/ATP carrier can be reversibly converted into a large channel by Ca2+","volume":"35","author":"Brustovetsky","year":"1996","journal-title":"Biochemistry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11804","DOI":"10.1021\/bi0200110","article-title":"A large Ca2+-dependent channel formed by recombinant ADP\/ATP carrier from Neurospora crassa resembles the mitochondrial permeability transition pore","volume":"41","author":"Brustovetsky","year":"2002","journal-title":"Biochemistry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"105447","DOI":"10.1016\/j.isci.2022.105447","article-title":"Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization","volume":"25","author":"Neginskaya","year":"2022","journal-title":"iScience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"eaaw4597","DOI":"10.1126\/sciadv.aaw4597","article-title":"Inhibition of mitochondrial permeability transition by deletion of the ANT family and CypD","volume":"5","author":"Karch","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13024-022-00547-7","article-title":"Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia","volume":"17","author":"Xia","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/S0006-3495(93)81336-5","article-title":"Probing alamethicin channels with water-soluble polymers. Effect on conductance of channel states","volume":"64","author":"Bezrukov","year":"1993","journal-title":"Biophys. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15652","DOI":"10.1074\/jbc.RA118.002926","article-title":"Deletion of mitochondrial calcium uniporter incompletely inhibits calcium uptake and induction of the permeability transition pore in brain mitochondria","volume":"293","author":"Hamilton","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/BF01868720","article-title":"Membrane potential of mitochondria measured with an electrode sensitive to tetraphenyl phosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state","volume":"49","author":"Kamo","year":"1979","journal-title":"J. Membr. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/jnr.22295","article-title":"Calpain activation and Na+\/Ca2+ exchanger degradation occur downstream of calcium deregulation in hippocampal neurons exposed to excitotoxic glutamate","volume":"88","author":"Brustovetsky","year":"2010","journal-title":"J. Neurosci. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"14202","DOI":"10.1016\/S0021-9258(18)77287-6","article-title":"Structure-function studies of adenine nucleotide transport in mitochondria. II. Biochemical analysis of distinct AAC1 and AAC2 proteins in yeast","volume":"265","author":"Gawaz","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/0014-5793(87)80442-8","article-title":"A membrane fusion strategy for single-channel recordings of membranes usually non-accessible to patch-clamp pipette electrodes","volume":"224","author":"Criado","year":"1987","journal-title":"FEBS Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"29481","DOI":"10.1016\/S0021-9258(18)43905-1","article-title":"Ion channel properties of the reconstituted chloroplast triose phosphate\/phosphate translocator","volume":"269","author":"Schwarz","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0005-2736(91)90295-J","article-title":"Small-volume extrusion apparatus for preparation of large, unilamellar vesicles","volume":"1061","author":"MacDonald","year":"1991","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"31375","DOI":"10.1074\/jbc.M109.009951","article-title":"An atypical role for collapsin response mediator protein 2 (CRMP-2) in neurotransmitter release via interaction with presynaptic voltage-gated calcium channels","volume":"284","author":"Brittain","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1080\/19336950.2017.1299838","article-title":"A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function","volume":"11","author":"Dustrude","year":"2017","journal-title":"Channels"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/0003-9861(79)90371-0","article-title":"The Ca2+-induced membrane transition in mitochondria. I. The protective mechanisms","volume":"195","author":"Hunter","year":"1979","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"12005","DOI":"10.1073\/pnas.0505294102","article-title":"Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia","volume":"102","author":"Schinzel","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/BF00762419","article-title":"Action of cyclosporine on mitochondrial calcium fluxes","volume":"19","author":"Fournier","year":"1987","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_50","first-page":"357","article-title":"Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress","volume":"255","author":"Crompton","year":"1988","journal-title":"Biochem. J."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Brustovetsky, T., Khanna, R., and Brustovetsky, N. (2023). CRMP2 participates in regulating mitochondrial morphology and motility in Alzheimer\u2019s disease. Cells, 12.","DOI":"10.3390\/cells12091287"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0014-5793(98)00317-2","article-title":"Reconstituted adenine nucleotide translocase forms a channel for small molecules comparable to the mitochondrial permeability transition pore","volume":"426","author":"Ruck","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.bbabio.2009.01.014","article-title":"Adenine nucleotide translocator 1 deficiency increases resistance of mouse brain and neurons to excitotoxic insults","volume":"1787","author":"Lee","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.yjmcc.2020.05.014","article-title":"Molecular nature and regulation of the mitochondrial permeability transition pore(s), drug target(s) in cardioprotection","volume":"144","author":"Carraro","year":"2020","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1073\/pnas.1921035117","article-title":"Mechanisms for Ca2+-dependent permeability transition in mitochondria","volume":"117","author":"Bernardi","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"A3","DOI":"10.1016\/j.yjmcc.2020.05.012","article-title":"A 20\/20 view of ANT function in mitochondrial biology and necrotic cell death","volume":"144","author":"Bround","year":"2020","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.celrep.2018.12.033","article-title":"ATP Synthase C-Subunit-Deficient Mitochondria Have a Small Cyclosporine A-Sensitive Channel, but Lack the Permeability Transition Pore","volume":"26","author":"Neginskaya","year":"2019","journal-title":"Cell Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7051","DOI":"10.1111\/febs.16254","article-title":"The mitochondrial permeability transition: Recent progress and open questions","volume":"289","author":"Bernardi","year":"2022","journal-title":"FEBS J."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Brustovetsky, N. (2020). The Role of Adenine Nucleotide Translocase in the Mitochondrial Permeability Transition. Cells, 9.","DOI":"10.3390\/cells9122686"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"749","DOI":"10.2217\/fnl.12.68","article-title":"Opening Pandora\u2019s jar: A primer on the putative roles of CRMP2 in a panoply of neurodegenerative, sensory and motor neuron, and central disorders","volume":"7","author":"Khanna","year":"2012","journal-title":"Future Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cell.2004.11.012","article-title":"GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity","volume":"120","author":"Yoshimura","year":"2005","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","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\u2019s disease","volume":"10","author":"Uchida","year":"2005","journal-title":"Genes Cells"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3134","DOI":"10.1021\/bi051635j","article-title":"Cyclin-dependent protein kinase 5 primes microtubule-associated protein tau site-specifically for glycogen synthase kinase 3beta","volume":"45","author":"Li","year":"2006","journal-title":"Biochemistry"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.bbrc.2016.04.012","article-title":"PPARgamma agonist pioglitazone improves cerebellar dysfunction at pre-Abeta deposition stage in APPswe\/PS1dE9 Alzheimer\u2019s disease model mice","volume":"473","author":"Toba","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yang, Z., Kuboyama, T., and Tohda, C. (2017). A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer\u2019s Disease and Its Target Molecule. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00340"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0300-9084(02)01366-4","article-title":"The adenine nucleotide translocator in apoptosis","volume":"84","author":"Belzacq","year":"2002","journal-title":"Biochimie"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nature02229","article-title":"The ADP\/ATP translocator is not essential for the mitochondrial permeability transition pore","volume":"427","author":"Kokoszka","year":"2004","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.abb.2004.01.013","article-title":"Quantitative evaluation of the effects of mitochondrial permeability transition pore modifiers on accumulation of calcium phosphate: Comparison of rat liver and brain mitochondria","volume":"424","author":"Panov","year":"2004","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5887","DOI":"10.1073\/pnas.1217823110","article-title":"Dimers of mitochondrial ATP synthase form the permeability transition pore","volume":"110","author":"Giorgio","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10580","DOI":"10.1073\/pnas.1401591111","article-title":"An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore","volume":"111","author":"Alavian","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/2\/179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T10:08:26Z","timestamp":1768817306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/2\/179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,19]]},"references-count":70,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["cells15020179"],"URL":"https:\/\/doi.org\/10.3390\/cells15020179","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,19]]}}}