{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:33:22Z","timestamp":1792805602584,"version":"4.5.0"},"reference-count":67,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002160","name":"Jain Foundation","doi-asserted-by":"crossref","award":["25TTV1"],"award-info":[{"award-number":["25TTV1"]}],"id":[{"id":"10.13039\/100002160","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Wayne State University Research","award":["221730"],"award-info":[{"award-number":["221730"]}],"id":[{"id":"https:\/\/ror.org\/01070mq45","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH","award":["R01 DC004076"],"award-info":[{"award-number":["R01 DC004076"]}]},{"name":"NIH","award":["R01 DC000156"],"award-info":[{"award-number":["R01 DC000156"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Dysferlin direct protein\u2013protein interactions (PPI) previously have been elucidated with surface plasmon resonance (SPR) and predicted to underlie membrane repair in mechanotransducing myofibrils. In mechanotransducing inner ear hair cells, dysferlin is detected with Z-stack confocal immunofluorescence in the stereocilia and their inserts in the tectorial membrane (TM) co-localizing with FKBP8, consistent with the SPR determination of tight, positively Ca2+-dependent interaction. FKBP8, a direct binding partner of mechanotransducing TMC1, when overexpressed, evokes an elevation in anti-apoptotic BCL2, inhibition of ryanodine receptor (RYR) activity, and a consequent reduction in Ca2+ release. RYR3 has now been immunolocalized to the tip of the TM in close association with a third-row outer hair cell (OHC) stereociliary BCL2-positive insertion. Dysferlin, annexin A2, and Alzheimer\u2019s proteins BACE1 and amyloid precursor protein (APP) are also accumulated in these stereociliary insertions. RYR2 and RYR1 have been immunolocalized to the TM core, in position to influence TM Ca2+. Dysferlin PPI pathways also intersect with AD protein pathways in the spiral ganglion (SG). Dysferlin segregates with FKBP8, BACE1, and RYR3 in the interiors of SG type I cell bodies. RYR1, RYR2, PSEN1, BCL2, and caspase 3 are primarily confined to plasma membrane sites. RYR3 pathways traverse the plasma membrane to the cell body interior. Western analysis of dysferlinopathy proteins links FKBP8 and BCL2 overexpression with RYR inhibition, indicative of dysferlin targets that are ameliorative in AD.<\/jats:p>","DOI":"10.3390\/ijms26199559","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"9559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dysferlin Protein\u2013Protein Interaction Pathways in the Organ of Corti and Spiral Ganglion Intersect with Alzheimer\u2019s Protein Pathways"],"prefix":"10.3390","volume":"26","author":[{"given":"Marian J.","family":"Drescher","sequence":"first","affiliation":[{"name":"Laboratory of Bio-Otology, Department of Otolaryngology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis G.","family":"Drescher","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Otology, Department of Otolaryngology, Wayne State University School of Medicine, Detroit, MI 48201, USA"},{"name":"Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid M.","family":"Khan","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Otology, Department of Otolaryngology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Hatfield","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Otology, Department of Otolaryngology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darshi","family":"Hemani","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Otology, Department of Otolaryngology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nature01573","article-title":"Defective membrane repair in dysferlin-deficient muscular dystrophy","volume":"423","author":"Bansal","year":"2003","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4707","DOI":"10.3390\/ijms24054707","article-title":"Analysis of dysferlin direct interactions with putative repair proteins links apoptotic signaling to Ca2+ elevation via PDCD6 and FKBP8","volume":"24","author":"Drescher","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref_3","unstructured":"Heidrych, P. (2008). Novel Interaction Partners for Otoferlin, a Functional Member of Acoustic Transmission in the Inner Ear. [Ph.D. Thesis, University of Tubingen]."},{"key":"ref_4","unstructured":"Labay, V., and Griffith, A. (2009, January 15). Identification of proteins that interact with TMC1 protein in the inner ear. Proceedings of the Association for Research in Otolaryngology, Baltimore, MD, USA."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1159\/000335789","article-title":"Temporal expression pattern of FKBP8 in rodent cochlea","volume":"28","author":"Zak","year":"2011","journal-title":"Cell Physiol. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/ncb894","article-title":"Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis","volume":"5","author":"Shirane","year":"2003","journal-title":"Nat. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19665","DOI":"10.1074\/jbc.M111.317214","article-title":"The FKBP38 catalytic domain binds to Bcl-2 via a charge-sensitive loop","volume":"287","author":"Haupt","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_8","first-page":"2782","article-title":"Bcl-2 binds to and inhibits ryanodine receptors","volume":"127","author":"Vervliet","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1113\/JP280905","article-title":"MET currents and otoacoustic emissions from mice with a detached tectorial membrane indicate the extracellular matrix regulates Ca2+ near stereocilia","volume":"599","author":"Jeng","year":"2021","journal-title":"Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107913","DOI":"10.1016\/j.heares.2020.107913","article-title":"Calcium signaling in interdental cells during the critical developmental period of the mouse cochlea","volume":"389","author":"Eckrich","year":"2020","journal-title":"Hear. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"427","DOI":"10.18632\/aging.100899","article-title":"Expression of amyloid-\u03b2 in mouse cochlear hair cells causes an early onset auditory defect in high-frequency sound perception","volume":"8","author":"Omata","year":"2016","journal-title":"Aging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/gbb.12370","article-title":"Reduced acoustic startle response and peripheral hearing loss in the 5xFAD mouse model of Alzheimer\u2019s disease","volume":"16","author":"Shin","year":"2017","journal-title":"Genes Brain Behav."},{"key":"ref_13","first-page":"2024","article-title":"Early-onset hearing loss in mouse models of Alzheimer\u2019s disease and increased DNA damage in the cochlea","volume":"1","author":"Par","year":"2024","journal-title":"Aging Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ibneur.2023.02.005","article-title":"Neuroprotective properties of anti-apoptotic BCL-2 proteins in 5xFAD mouse model of Alzheimer\u2019s disease","volume":"14","author":"Chernyuk","year":"2023","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9013","DOI":"10.1523\/JNEUROSCI.0028-19.2019","article-title":"\u03b2-Secretase BACE1 is required for normal cochlear function","volume":"39","author":"Dierich","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_16","unstructured":"Drescher, D.G., and Drescher, M.J. (2018, January 11). Noise-induced up-modulation of annexin A2 and dysferlin in stereocilia of cochlear outer hair cells. Proceedings of the Association for Research in Otolaryngology, San Diego, CA, USA."},{"key":"ref_17","unstructured":"Drescher, D.G., Drescher, M.J., and Annan, P. (2019, January 12). Dysferlin direct protein-protein interactions support involvement of dysferlin in apoptotic pathways of hair cells as predicted by structurally similar otoferlin. Proceedings of the Association for Research in Otolaryngology, Baltimore, MD, USA."},{"key":"ref_18","unstructured":"Drescher, M.J., and Drescher, D.G. (2025, January 23). Hair cell proteins in stereocilia embedded in the tectorial membrane: Dysferlin, annexin A2, FKBP8, Bcl2, and RyR3, forming a molecular pathway to regulate Ca2+. Proceedings of the Association for Research in Otolaryngology, Orlando, FL, USA."},{"key":"ref_19","unstructured":"Drescher, D.G., and Drescher, M.J. (2025, January 23). Molecular targeting of Alzheimer\u2019s disease-associated proteins in the spiral ganglion and cochlear neural components by dysferlin protein-protein interactions. Proceedings of the Association for Research in Otolaryngology, Orlando, FL, USA."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1042\/BCJ20160690","article-title":"Dopamine D1A directly interacts with otoferlin synaptic pathway proteins: Phosphorylation underlies a molecular switch from NSF to AP2mu1 interactions","volume":"474","author":"Selvakumar","year":"2017","journal-title":"Biochem. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00401-020-02234-7","article-title":"Accumulation of amyloid precursor protein C-terminal fragments triggers mitochondrial structure, function, and mitophagy defects in Alzheimer\u2019s disease models and human brains","volume":"141","author":"Mary","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Isei, M.O., Crockett, M., Chen, E., Rodwell-Bullock, J., Carroll, T., Girardi, P.A., Nehrke, K., and Johnson, G.V.W. (2025). Tau phosphorylation suppresses oxidative stress-induced mitophagy via FKBP8 receptor modulation. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0307358"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18195","DOI":"10.1074\/jbc.M000040200","article-title":"Presenilin-1 mutations increase levels of ryanodine receptors and calcium release in PC12 cells and cortical neurons","volume":"275","author":"Chan","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/s41431-023-01302-2","article-title":"Rare-variant association analysis reveals known and new age-related hearing loss genes","volume":"31","author":"Li","year":"2023","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1093\/hmg\/ddi195","article-title":"Interaction of presenilins with FKBP38 promotes apoptosis by reducing mitochondrial Bcl-2","volume":"14","author":"Wang","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1111\/jnc.16155","article-title":"Presenilin deficiency enhances tau phosphorylation and its secretion","volume":"168","author":"Sun","year":"2024","journal-title":"J. Neurochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7215","DOI":"10.1074\/jbc.M112.443226","article-title":"Cyclic nucleotide-gated channel \u03b1-3 (CNGA3) interacts with stereocilia tip-link cadherin 23 + exon 68 or alternatively with myosin VIIa, two proteins required for hair cell mechanotransduction","volume":"288","author":"Selvakumar","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0378-5955(92)90152-D","article-title":"Actin-binding and microtubule-associated proteins in the organ of Corti","volume":"51","author":"Slepecky","year":"1992","journal-title":"Hear. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"McInturff, S., Burns, J.C., and Kelley, M.W. (2018). Characterization of spatial and temporal development of Type I and Type II hair cells in the mouse utricle using new cell-type-specific markers. Biol. Open., 7.","DOI":"10.1242\/bio.038083"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Maphis, N., Xu, G., Kokiko-Cochran, O.N., Cardona, A.E., Ransohoff, R.M., Lamb, B.T., and Bhaskar, K. (2015). Loss of tau rescues inflammation-mediated neurodegeneration. Front. Neurosci., 9.","DOI":"10.3389\/fnins.2015.00196"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1021\/acschemneuro.6b00049","article-title":"Alzheimer\u2019s Amyloid-\u03b2 sequesters caspase-3 in vitro via its C-terminal tail","volume":"7","author":"Chang","year":"2016","journal-title":"ACS Chem. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9770","DOI":"10.1074\/jbc.M109.032466","article-title":"FKBP38 protects Bcl-2 from caspase-dependent degradation","volume":"285","author":"Choi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5756","DOI":"10.1073\/pnas.1805223116","article-title":"Control of hearing sensitivity by tectorial membrane calcium","volume":"116","author":"Strimbu","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1038\/s41467-021-22870-1","article-title":"Inner hair cell stereocilia are embedded in the tectorial membrane","volume":"12","author":"Hakizimana","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1002\/humu.22822","article-title":"Nonsyndromic early-onset cone-rod dystrophy and limb-girdle muscular dystrophy in a consanguineous Israeli family are caused by two independent yet linked mutations in ALMS1 and DYSF","volume":"36","author":"Lazar","year":"2015","journal-title":"Hum. Mutat."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00401-006-0147-8","article-title":"The muscle protein dysferlin accumulates in the Alzheimer brain","volume":"112","author":"Galvin","year":"2006","journal-title":"Acta Neuropathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15091","DOI":"10.1073\/pnas.1304171110","article-title":"Presenilins regulate calcium homeostasis and presynaptic function via ryanodine receptors in hippocampal neurons","volume":"110","author":"Wu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.cmet.2020.07.017","article-title":"A high-density human mitochondrial proximity interaction network","volume":"32","author":"Antonicka","year":"2020","journal-title":"Cell Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41419-024-06742-2","article-title":"The amyloid precursor protein and its derived fragments concomitantly contribute to the alterations of mitochondrial transport machinery in Alzheimer\u2019s disease","volume":"15","author":"Eysert","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3233\/JAD-215280","article-title":"Mitochondrial membrane potential influences amyloid precursor protein localization and A\u03b2secretion","volume":"85","author":"Wilkins","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/neu.20006","article-title":"Overexpression of Bcl-2 prevents neomycin-induced hair cell death and caspase-9 activation in the adult mouse utricle in vitro","volume":"60","author":"Cunningham","year":"2004","journal-title":"J. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11160","DOI":"10.1523\/JNEUROSCI.3674-04.2004","article-title":"A \u201csynaptoplasmic cistern\u201d mediates rapid inhibition of cochlear hair cells","volume":"24","author":"Lioudyno","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1111\/j.1460-9568.2005.04310.x","article-title":"Ryanodine receptors and BK channels act as a presynaptic depressor of neurotransmission in cochlear inner hair cells","volume":"22","author":"Beurg","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s10162-007-0090-y","article-title":"Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cells","volume":"8","author":"Ballestero","year":"2007","journal-title":"JARO"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1152\/jn.00097.2020","article-title":"Nicotine evoked efferent transmitter release onto immature cochlea inner hair cells","volume":"124","author":"Zhang","year":"2020","journal-title":"J. Neurophysiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.1523\/JNEUROSCI.0230-18.2018","article-title":"Voltage-gated calcium influx modifies cholinergic inhibition of inner hair cells in the immature rat cochlea","volume":"38","author":"Zachary","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.heares.2006.06.002","article-title":"Ryanodine receptor localization in the mammalian cochlea; An ultrastructural study","volume":"219","author":"Grant","year":"2006","journal-title":"Hear. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.4081\/ejh.2009.e30","article-title":"Differential expression of ryanodine receptor in the developing rat cochlea","volume":"53","author":"Liang","year":"2009","journal-title":"Eur. J. Histochem."},{"key":"ref_49","first-page":"10506","article-title":"Structural and functional interactions between the EF hand domain and S2\u2013S3 loop in the type-1 ryanodine receptor ion channel","volume":"300","author":"Chirasani","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6335","DOI":"10.1096\/fj.201901951RR","article-title":"Potential contribution of ryanodine receptor 2 upregulation to cGMP\/PKG signaling-induced cone degeneration in cyclic nucleotide-gated channel deficiency","volume":"34","author":"Yang","year":"2020","journal-title":"FASEB J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1161\/CIRCRESAHA.124.324588","article-title":"Dysferlin enables tubular membrane proliferation in cardiac hypertrophy","volume":"135","author":"Paulke","year":"2024","journal-title":"Circ. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/2044-5040-3-3","article-title":"A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome","volume":"3","author":"Blandin","year":"2013","journal-title":"Skelet. Muscle"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.neuroscience.2005.09.011","article-title":"Differential expression of ryanodine receptors in the rat cochlea","volume":"137","author":"Cannell","year":"2006","journal-title":"Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e70099","DOI":"10.1096\/fj.202401731RR","article-title":"Plasma membrane repair defect in Alzheimer\u2019s disease neurons is driven by the reduced dysferlin expression","volume":"38","author":"Bulgart","year":"2024","journal-title":"FASEB J."},{"key":"ref_55","first-page":"11820","article-title":"Ryanodine receptor blockade reduces amyloid-load and memory impairments in Tg2576 mouse model of Alzheimer disease","volume":"201232","author":"Greco","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1750-1326-9-21","article-title":"Ryanodine receptors: Physiological function and deregulation in Alzheimer disease","volume":"9","author":"Checler","year":"2014","journal-title":"Mol. Neurodegener."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e162891","DOI":"10.1172\/JCI162891","article-title":"Targeting ryanodine receptors to treat human diseases","volume":"133","author":"Marks","year":"2023","journal-title":"Review. J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s40478-025-02023-x","article-title":"Mitochondrial dysfunction mediated by ER-calcium dysregulation in neurons derived from Alzheimer\u2019s disease patients","volume":"13","author":"Gallegos","year":"2025","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.14336\/AD.2022.0204","article-title":"Age-related loss of miR-124 causes cognitive deficits via derepressing RyR3 expression","volume":"13","author":"Liu","year":"2022","journal-title":"Aging Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s11011-024-01371-2","article-title":"Rosuvastatin attenuates total-tau serum levels and increases expression of miR-124-3p in dyslipidemic Alzheimer\u2019s patients: A historic cohort study","volume":"39","author":"Usefi","year":"2024","journal-title":"Metab. Brain Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.expneurol.2013.09.001","article-title":"Presenilins regulate the cellular activity of ryanodine receptors differentially through isotype-specific N-terminal cysteines","volume":"250","author":"Payne","year":"2013","journal-title":"Exp. Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s00401-013-1186-6","article-title":"Dysferlin is a newly identified binding partner of A\u03b2PP and it co-aggregates with amyloid-\u03b242 within sporadic inclusion-bodymyositis (s-IBM) muscle fibers","volume":"126","author":"Cacciottolo","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Lloyd, E.M., Pinniger, G.J., Grounds, M.D., and Murphy, R.M. (2022). Dysferlin deficiency results in myofiber-type specific differences in abundances of calcium-handling and glycogen metabolism proteins. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010076"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"18038","DOI":"10.1016\/j.heares.2020.108038","article-title":"Does hearing loss lead to dementia? A review of the literature","volume":"402","author":"Nadhimi","year":"2021","journal-title":"Hear. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"61","DOI":"10.4103\/CJP.CJP_79_20","article-title":"Tau phosphorylation and cochlear apoptosis cause hearing loss in 3xTg-AD mouse model of Alzheimer\u2019s disease","volume":"64","author":"Wang","year":"2021","journal-title":"Chin. J. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lanner, J.T., Georgiou, D.K., Joshi, A.D., and Hamilton, S.L. (2010). Ryanodine receptors: Structure, expression, molecular details, and function in calcium release. Cold Spring Harb. Perspect. Biol., 2.","DOI":"10.1101\/cshperspect.a003996"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"313","DOI":"10.2174\/1567205017666200225102941","article-title":"Targeting post-translational remodeling of ryanodine receptor: A new track for Alzheimer\u2019s disease therapy?","volume":"17","author":"Chami","year":"2020","journal-title":"Curr. Alzheimer Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9559\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T04:24:26Z","timestamp":1759379066000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,30]]},"references-count":67,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms26199559"],"URL":"https:\/\/doi.org\/10.3390\/ijms26199559","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,30]]}}}