{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:09:49Z","timestamp":1760144989835,"version":"build-2065373602"},"reference-count":144,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Current Research Funds 2025","doi-asserted-by":"publisher","award":["RRC-2025-23686388"],"award-info":[{"award-number":["RRC-2025-23686388"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD), the most prevalent form of dementia, poses a critical global health challenge as its incidence rises with aging populations. Despite extensive research into its genetic and molecular underpinnings, effective therapeutic strategies remain limited. Growing evidence suggests that physical exercise may offer neuroprotective benefits, potentially mitigating AD progression through multifactorial mechanisms. This review synthesizes current findings on the interplay between aerobic exercise and AD pathophysiology, with a focus on amyloid-\u03b2 (A\u03b2) metabolism, gene expression, and neuroinflammation. We explore how exercise influences A\u03b2 clearance, modulates amyloid precursor protein (APP) processing, and impacts the activity of key enzymes such as secretases and neprilysin. Further, we highlight the gene\u2013exercise crosstalk identified through transcriptomic data, particularly in the entorhinal cortex\u2014an early site of A\u03b2 deposition. Our analysis also discusses how exercise-induced modulation of molecular pathways\u2014including mitochondrial function, oxidative stress responses, and neuroinflammatory cascades\u2014may confer cognitive resilience. By integrating molecular, genetic, and systems biology data, this review underscores the potential of structured physical activity as a non-pharmacological intervention to delay or attenuate AD pathology. These insights support a precision medicine approach, which combines lifestyle interventions with molecular profiling, to improve prevention strategies and therapeutic outcomes in AD.<\/jats:p>","DOI":"10.3390\/ijms26199816","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:50:16Z","timestamp":1760107816000},"page":"9816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gene-Exercise Interactions in Amyloid Metabolism and Clearance: Implications for Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7882-2432","authenticated-orcid":false,"given":"Maria Francesca","family":"Astorino","sequence":"first","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morpho-Functional Imaging\u2014BIOMORF, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-1455","authenticated-orcid":false,"given":"Giovanni Luca","family":"Cipriano","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Anchesi","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3694-5287","authenticated-orcid":false,"given":"Maria","family":"Lui","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3999-0286","authenticated-orcid":false,"given":"Ivana","family":"Raffaele","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2082-9855","authenticated-orcid":false,"given":"Marco","family":"Calabr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morpho-Functional Imaging\u2014BIOMORF, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9703-0083","authenticated-orcid":false,"given":"Concetta","family":"Crisafulli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morpho-Functional Imaging\u2014BIOMORF, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mertas, B., and Bosgelmez, I.I. (2025). The Role of Genetic, Environmental, and Dietary Factors in Alzheimer\u2019s Disease: A Narrative Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031222"},{"key":"ref_2","first-page":"3708","article-title":"Alzheimer\u2019s disease facts and figures","volume":"20","author":"Better","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijbiomac.2021.08.197","article-title":"The role of amyloids in Alzheimer\u2019s and Parkinson\u2019s diseases","volume":"190","author":"Salahuddin","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1080\/07853890.2022.2074535","article-title":"Global, regional and national burden of gastroesophageal reflux disease, 1990\u20132019: Update from the GBD 2019 study","volume":"54","author":"Zhang","year":"2022","journal-title":"Ann. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3934\/Neuroscience.2021005","article-title":"The biological pathways of Alzheimer disease: A review","volume":"8","author":"Calabro","year":"2021","journal-title":"AIMS Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1097\/WCO.0000000000001242","article-title":"Recent advances in Alzheimer disease genetics","volume":"37","author":"Nicolas","year":"2024","journal-title":"Curr. Opin. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.arcmed.2012.10.017","article-title":"Genetics of Alzheimer\u2019s disease","volume":"43","year":"2012","journal-title":"Arch. Med. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.12779\/dnd.2018.17.4.131","article-title":"Genetics of Alzheimer\u2019s Disease","volume":"17","author":"Kim","year":"2018","journal-title":"Dement. Neurocogn. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.abb.2007.05.014","article-title":"Protein folding: Then and now","volume":"469","author":"Chen","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"55034","DOI":"10.12775\/JEHS.2024.67.55034","article-title":"Physical Exercise as a Strategy for Prevention and Management of Alzheimer\u2019s Disease Progression","volume":"67","author":"Haber","year":"2024","journal-title":"J. Educ. Health Sport"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3233\/JAD-2010-091531","article-title":"Exercise plays a preventive role against Alzheimer\u2019s disease","volume":"20","author":"Radak","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"403","DOI":"10.3892\/br.2016.607","article-title":"Role of physical exercise in Alzheimer\u2019s disease","volume":"4","author":"Chen","year":"2016","journal-title":"Biomed. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1007\/s11064-018-2571-2","article-title":"Treadmill Exercise Ameliorates Spatial Learning and Memory Deficits Through Improving the Clearance of Peripheral and Central Amyloid-Beta Levels","volume":"43","author":"Khodadadi","year":"2018","journal-title":"Neurochem. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"He, X.F., Liu, D.X., Zhang, Q., Liang, F.Y., Dai, G.Y., Zeng, J.S., Pei, Z., Xu, G.Q., and Lan, Y. (2017). Voluntary Exercise Promotes Glymphatic Clearance of Amyloid Beta and Reduces the Activation of Astrocytes and Microglia in Aged Mice. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00144"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1523\/JNEUROSCI.0496-05.2005","article-title":"Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer\u2019s disease","volume":"25","author":"Adlard","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_16","first-page":"959","article-title":"Physical activity and beta-amyloid pathology in Alzheimer\u2019s disease: A sound mind in a sound body","volume":"16","author":"Ebrahimi","year":"2017","journal-title":"EXCLI J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jshs.2020.08.009","article-title":"Physical exercise may exert its therapeutic influence on Alzheimer\u2019s disease through the reversal of mitochondrial dysfunction via SIRT1-FOXO1\/3-PINK1-Parkin-mediated mitophagy","volume":"10","author":"Zhao","year":"2021","journal-title":"J. Sport Health Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1249\/JSR.0000000000000332","article-title":"Alzheimer\u2019s Disease and Exercise: A Literature Review","volume":"16","author":"Cass","year":"2017","journal-title":"Curr. Sports Med. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Cutuli, D., Decandia, D., Giacovazzo, G., and Coccurello, R. (2023). Physical Exercise as Disease-Modifying Alternative against Alzheimer\u2019s Disease: A Gut-Muscle-Brain Partnership. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914686"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111263","DOI":"10.1016\/j.brainresbull.2025.111263","article-title":"Aerobic exercise improves clearance of amyloid-beta via the glymphatic system in a mouse model of Alzheimer\u2019s Disease","volume":"222","author":"Liang","year":"2025","journal-title":"Brain Res. Bull."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pahlavani, H.A. (2023). Exercise therapy to prevent and treat Alzheimer\u2019s disease. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1243869"},{"key":"ref_22","first-page":"D77","article-title":"Expression Atlas update: From tissues to single cells","volume":"48","author":"Papatheodorou","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0140-6736(24)01296-0","article-title":"Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission","volume":"404","author":"Livingston","year":"2024","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1289\/ehp.7651","article-title":"Personalized exposure assessment: Promising approaches for human environmental health research","volume":"113","author":"Weis","year":"2005","journal-title":"Environ. Health Perspect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1080\/07315724.2019.1683379","article-title":"Alzheimer\u2019s Disease and Parkinson\u2019s Disease: A Nutritional Toxicology Perspective of the Impact of Oxidative Stress, Mitochondrial Dysfunction, Nutrigenomics and Environmental Chemicals","volume":"39","author":"Agnihotri","year":"2020","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3233\/JAD-2002-4308","article-title":"The significance of environmental factors in the etiology of Alzheimer\u2019s disease","volume":"4","author":"Grant","year":"2002","journal-title":"J. Alzheimers Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lopez-Ortiz, S., Pinto-Fraga, J., Valenzuela, P.L., Martin-Hernandez, J., Seisdedos, M.M., Garcia-Lopez, O., Toschi, N., Di Giuliano, F., Garaci, F., and Mercuri, N.B. (2021). Physical Exercise and Alzheimer\u2019s Disease: Effects on Pathophysiological Molecular Pathways of the Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062897"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e374","DOI":"10.1212\/WNL.0000000000009816","article-title":"Healthy lifestyle and the risk of Alzheimer dementia: Findings from 2 longitudinal studies","volume":"95","author":"Dhana","year":"2020","journal-title":"Neurology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e072691","DOI":"10.1136\/bmj-2022-072691","article-title":"Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study","volume":"380","author":"Jia","year":"2023","journal-title":"BMJ"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0140-6736(12)61031-9","article-title":"Effect of physical inactivity on major non-communicable diseases worldwide: An analysis of burden of disease and life expectancy","volume":"380","author":"Lee","year":"2012","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s13670-014-0101-x","article-title":"The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and Cardiovascular Disease","volume":"3","author":"Hayes","year":"2014","journal-title":"Curr. Geriatr. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jshs.2020.01.004","article-title":"Physical exercise in the prevention and treatment of Alzheimer\u2019s disease","volume":"9","author":"Millan","year":"2020","journal-title":"J. Sport Health Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1093\/gerona\/61.11.1166","article-title":"Aerobic exercise training increases brain volume in aging humans","volume":"61","author":"Colcombe","year":"2006","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3233\/JAD-150660","article-title":"A Comparative Study Evaluating the Impact of Physical Exercise on Disease Progression in a Mouse Model of Alzheimer\u2019s Disease","volume":"53","author":"Xhima","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.semcdb.2011.03.011","article-title":"Amyloid in neurodegenerative diseases: Friend or foe?","volume":"22","author":"Wolfe","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1186\/s12964-024-01791-8","article-title":"Misfolding and aggregation in neurodegenerative diseases: Protein quality control machinery as potential therapeutic clearance pathways","volume":"22","author":"Koszla","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1001\/archneurol.2007.56","article-title":"Protein misfolding and neurodegeneration","volume":"65","author":"Soto","year":"2008","journal-title":"Arch. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12411","DOI":"10.3390\/ijms140612411","article-title":"Protein folding and aggregation into amyloid: The interference by natural phenolic compounds","volume":"14","author":"Stefani","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hiroaki, H. (2023). Molecular mechanisms of amyloid-beta peptide fibril and oligomer formation: NMR-based challenges. Biophys. Physicobiol., 20.","DOI":"10.2142\/biophysico.bppb-v20.0007"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9812178","DOI":"10.1155\/2016\/9812178","article-title":"Metals and Neuronal Metal Binding Proteins Implicated in Alzheimer\u2019s Disease","volume":"2016","author":"Cristovao","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature02940","article-title":"Addendum: Pathways towards and away from Alzheimer\u2019s disease","volume":"431","author":"Mattson","year":"2004","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.1365-2796.2008.02068.x","article-title":"The emerging concept of functional amyloid","volume":"265","author":"Maury","year":"2009","journal-title":"J. Intern. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e22493","DOI":"10.1096\/fj.202200235R","article-title":"Interactions of amyloid coaggregates with biomolecules and its relevance to neurodegeneration","volume":"36","author":"Murakami","year":"2022","journal-title":"FASEB J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1097\/WNR.0000000000001230","article-title":"Treadmill exercise inhibits amyloid-beta generation in the hippocampus of APP\/PS1 transgenic mice by reducing cholesterol-mediated lipid raft formation","volume":"30","author":"Zhang","year":"2019","journal-title":"Neuroreport"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"111502","DOI":"10.1016\/j.exger.2021.111502","article-title":"Effect of involuntary chronic physical exercise on beta-amyloid protein in experimental models of Alzheimer\u2019s disease: Systematic review and meta-analysis","volume":"153","author":"Rocha","year":"2021","journal-title":"Exp. Gerontol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Sepulveda-Lara, A., Sepulveda, P., and Marzuca-Nassr, G.N. (2024). Resistance Exercise Training as a New Trend in Alzheimer\u2019s Disease Research: From Molecular Mechanisms to Prevention. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137084"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Vidoni, E.D., Morris, J.K., Watts, A., Perry, M., Clutton, J., Van Sciver, A., Kamat, A.S., Mahnken, J., Hunt, S.L., and Townley, R. (2021). Effect of aerobic exercise on amyloid accumulation in preclinical Alzheimer\u2019s: A 1-year randomized controlled trial. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0244893"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrneurol.2009.218","article-title":"The secretases: Enzymes with therapeutic potential in Alzheimer disease","volume":"6","author":"Vassar","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3922","DOI":"10.1073\/pnas.96.7.3922","article-title":"Constitutive and regulated alpha-secretase cleavage of Alzheimer\u2019s amyloid precursor protein by a disintegrin metalloprotease","volume":"96","author":"Lammich","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"29621","DOI":"10.1074\/jbc.R800015200","article-title":"The role of amyloid precursor protein processing by BACE1, the beta-secretase, in Alzheimer disease pathophysiology","volume":"283","author":"Cole","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.nurt.2008.05.010","article-title":"Inhibition and modulation of gamma-secretase for Alzheimer\u2019s disease","volume":"5","author":"Wolfe","year":"2008","journal-title":"Neurotherapeutics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4207","DOI":"10.1074\/jbc.M508445200","article-title":"A dominant role for FE65 (APBB1) in nuclear signaling","volume":"281","author":"Yang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/jnr.10834","article-title":"Isoform-specific knockout of FE65 leads to impaired learning and memory","volume":"75","author":"Wang","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Strecker, P., Ludewig, S., Rust, M., Mundinger, T.A., Gorlich, A., Krachan, E.G., Mehrfeld, C., Herz, J., Korte, M., and Guenette, S.Y. (2016). FE65 and FE65L1 share common synaptic functions and genetically interact with the APP family in neuromuscular junction formation. Sci. Rep., 6.","DOI":"10.1038\/srep25652"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Santiago, J.A., Quinn, J.P., and Potashkin, J.A. (2022). Physical Activity Rewires the Human Brain against Neurodegeneration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116223"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1091\/mbc.E19-09-0487","article-title":"Distinct anterograde trafficking pathways of BACE1 and amyloid precursor protein from the TGN and the regulation of amyloid-beta production","volume":"31","author":"Tan","year":"2020","journal-title":"Mol. Biol. Cell"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Covington, J.D., Galgani, J.E., Moro, C., LaGrange, J.M., Zhang, Z., Rustan, A.C., Ravussin, E., and Bajpeyi, S. (2014). Skeletal muscle perilipin 3 and coatomer proteins are increased following exercise and are associated with fat oxidation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091675"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1254\/fpj.22081","article-title":"Identification of novel regulators involved in AD pathogenesis using the CRISPR-Cas9 system","volume":"158","author":"Tomizawa","year":"2023","journal-title":"Nihon Yakurigaku Zasshi"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7504","DOI":"10.1074\/jbc.M608088200","article-title":"gamma-Secretase-mediated release of the low density lipoprotein receptor-related protein 1B intracellular domain suppresses anchorage-independent growth of neuroglioma cells","volume":"282","author":"Liu","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.exer.2016.10.013","article-title":"The Alzheimer\u2019s-related amyloid beta peptide is internalised by R28 neuroretinal cells and disrupts the microtubule associated protein 2 (MAP-2)","volume":"153","author":"Lynn","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Takahashi, R.H., Capetillo-Zarate, E., Lin, M.T., Milner, T.A., and Gouras, G.K. (2013). Accumulation of intraneuronal beta-amyloid 42 peptides is associated with early changes in microtubule-associated protein 2 in neurites and synapses. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0051965"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.bbr.2016.04.029","article-title":"Distinct neuroplasticity processes are induced by different periods of acrobatic exercise training","volume":"308","author":"Salame","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"49976","DOI":"10.1074\/jbc.M210179200","article-title":"Nectin-1alpha, an immunoglobulin-like receptor involved in the formation of synapses, is a substrate for presenilin\/gamma-secretase-like cleavage","volume":"277","author":"Kim","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Du, F., Yu, Q., Hu, G., Lin, C.S., and ShiDu Yan, S. (2025). PINK1-dependent NFKB signaling contributes to amyloid pathology in Alzheimer disease. Autophagy, 1\u201317.","DOI":"10.1080\/15548627.2025.2463322"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Munoz, V.R., Vieira, R.F.L., Katashima, C.K., Gaspar, R.C., Lino, M., Trombeta, J., Duft, R.G., Azevedo Macedo, A.P., da Silva, A.S.R., and Ropelle, E.R. (2024). Rho-Kinase Is Differentially Expressed in the Adipose Tissue of Rodent and Human in Response to Aging, Sex, and Acute Exercise. J. Gerontol. Ser. A Biol. Sci. Med. Sci., 79.","DOI":"10.1093\/gerona\/glae001"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"C1123","DOI":"10.1152\/ajpcell.00070.2019","article-title":"Regulatory function of praja ring finger ubiquitin ligase 2 mediated by the P2rx3\/P2rx7 axis in mouse hippocampal neuronal cells","volume":"318","author":"Gong","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"ra47","DOI":"10.1126\/scisignal.aaf6209","article-title":"Gain-of-function mutations in protein kinase Calpha (PKCalpha) may promote synaptic defects in Alzheimer\u2019s disease","volume":"9","author":"Alfonso","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1016\/j.bbamem.2009.05.015","article-title":"Calcium enhances the proteolytic activity of BACE1: An in vitro biophysical and biochemical characterization of the BACE1-calcium interaction","volume":"1788","author":"Hayley","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"10153","DOI":"10.1074\/jbc.M116.743070","article-title":"Amyloid beta production is regulated by beta2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor","volume":"292","author":"Bussiere","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_70","first-page":"e10311","article-title":"Upregulation of Ryanodine Receptor Calcium Channels (RyR2) in Rats with Induced Diabetes after 4 Weeks of High Intensity Interval Training","volume":"10","author":"Faramarzi","year":"2016","journal-title":"Int. Cardiovasc. Res. J."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Overby, M., Serrano-Rodriguez, A., Dadras, S., Christiansen, A.K., Ozcelik, G., Lichtenthaler, S.F., Weick, J.P., and Muller, H.K. (2023). Neuron-specific gene NSG1 binds to and positively regulates sortilin ectodomain shedding via a metalloproteinase-dependent mechanism. J. Biol. Chem., 299.","DOI":"10.1016\/j.jbc.2023.105446"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Berrocal, M., Saez, L., and Mata, A.M. (2021). Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer\u2019s Disease on the Pump Activity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116055"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"51100","DOI":"10.1074\/jbc.M309561200","article-title":"Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by FE65L1","volume":"278","author":"Chang","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/jnr.21548","article-title":"Amyloid beta-peptide activates nuclear factor-kappaB through an N-methyl-D-aspartate signaling pathway in cultured cerebellar cells","volume":"86","author":"Kawamoto","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Xu, H., Tian, X., Wang, Y., Lin, J., Zhu, B., Zhao, C., Wang, B., Zhang, X., Sun, Y., and Li, N. (2024). Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin\/TLR4\/MyD88\/NF-kappaB-Mediated Neuroinflammation Pathway. Biology, 13.","DOI":"10.3390\/biology13100809"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1038\/s41418-020-0584-2","article-title":"Loss of Ryanodine Receptor 2 impairs neuronal activity-dependent remodeling of dendritic spines and triggers compensatory neuronal hyperexcitability","volume":"27","author":"Bertan","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1089\/ars.2010.3287","article-title":"Amyloid beta-peptide oligomers stimulate RyR-mediated Ca2+ release inducing mitochondrial fragmentation in hippocampal neurons and prevent RyR-mediated dendritic spine remodeling produced by BDNF","volume":"14","author":"Adasme","year":"2011","journal-title":"Antioxid. Antioxid. Redox Signal."},{"key":"ref_78","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_79","doi-asserted-by":"crossref","unstructured":"Vervliet, T. (2018). Ryanodine Receptors in Autophagy: Implications for Neurodegenerative Diseases?. Front. Cell Neurosci., 12.","DOI":"10.3389\/fncel.2018.00089"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1177\/1073858419882619","article-title":"Amyloid, APP, and Electrical Activity of the Brain","volume":"26","author":"Hefter","year":"2020","journal-title":"Neuroscientist"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1756-6606-4-3","article-title":"APP processing in Alzheimer\u2019s disease","volume":"4","author":"Zhang","year":"2011","journal-title":"Mol. Brain"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Karisetty, B.C., Bhatnagar, A., Armour, E.M., Beaver, M., Zhang, H., and Elefant, F. (2020). Amyloid-beta Peptide Impact on Synaptic Function and Neuroepigenetic Gene Control Reveal New Therapeutic Strategies for Alzheimer\u2019s Disease. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.577622"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Ding, Y., Zhao, J., Zhang, X., Wang, S., Viola, K.L., Chow, F.E., Zhang, Y., Lippa, C., Klein, W.L., and Gong, Y. (2019). Amyloid Beta Oligomers Target to Extracellular and Intracellular Neuronal Synaptic Proteins in Alzheimer\u2019s Disease. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.01140"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/s41419-019-1636-8","article-title":"Abeta oligomers promote oligodendrocyte differentiation and maturation via integrin beta1 and Fyn kinase signaling","volume":"10","author":"Valero","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1755-5949.2010.00221.x","article-title":"The upside of APP at synapses","volume":"18","author":"Hoe","year":"2012","journal-title":"CNS Neurosci. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Lee, L.C., Goh, M.Q.L., and Koo, E.H. (2017). Transcriptional regulation of APP by apoE: To boldly go where no isoform has gone before: ApoE, APP transcription and AD: Hypothesised mechanisms and existing knowledge gaps. Bioessays, 39.","DOI":"10.1002\/bies.201700062"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1749-6632.2000.tb06934.x","article-title":"Regulation of APP synthesis and secretion by neuroimmunophilin ligands and cyclooxygenase inhibitors","volume":"920","author":"Lee","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Sato, K., Takayama, K.I., Hashimoto, M., and Inoue, S. (2021). Transcriptional and Post-Transcriptional Regulations of Amyloid-beta Precursor Protein (APP) mRNA. Front. Aging, 2.","DOI":"10.3389\/fragi.2021.721579"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Cha, H.J., Shen, J., and Kang, J. (2022). Regulation of gene expression by the APP family in the adult cerebral cortex. Sci. Rep., 12.","DOI":"10.1038\/s41598-021-04027-8"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mcn.2017.11.008","article-title":"Exercise decreases BACE and APP levels in the hippocampus of a rat model of Alzheimer\u2019s disease","volume":"86","author":"Alkadhi","year":"2018","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Bartra, C., Jager, L.A., Alcarraz, A., Meza-Ramos, A., Sanguesa, G., Corpas, R., Guasch, E., Batlle, M., and Sanfeliu, C. (2022). Antioxidant Molecular Brain Changes Parallel Adaptive Cardiovascular Response to Forced Running in Mice. Antioxidants, 11.","DOI":"10.3390\/antiox11101891"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Lu, J., Wang, J., Yu, L., Cui, R., Zhang, Y., Ding, H., and Yan, G. (2021). Treadmill Exercise Attenuates Cerebral Ischemia-Reperfusion Injury by Promoting Activation of M2 Microglia via Upregulation of Interleukin-4. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.735485"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1007\/s12640-010-9170-6","article-title":"Amyloid-beta precursor protein induces glial differentiation of neural progenitor cells by activation of the IL-6\/gp130 signaling pathway","volume":"18","author":"Kwak","year":"2010","journal-title":"Neurotox. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1523\/JNEUROSCI.3316-06.2007","article-title":"Protein phosphatase 2A methyltransferase links homocysteine metabolism with tau and amyloid precursor protein regulation","volume":"27","author":"Sontag","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Jian, Y., Yuan, S., Yang, J., Lei, Y., Li, X., and Liu, W. (2022). Aerobic Exercise Alleviates Abnormal Autophagy in Brain Cells of APP\/PS1 Mice by Upregulating AdipoR1 Levels. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179921"},{"key":"ref_96","first-page":"e69450","article-title":"A Review on the Role of SNCA Gene in Neurodegenerative Diseases","volume":"16","author":"Jahabardeen","year":"2024","journal-title":"Cureus"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"149506","DOI":"10.1016\/j.brainres.2025.149506","article-title":"The alpha-MG exhibits neuroprotective potential by reducing amyloid beta peptide-induced inflammation, oxidative stress, and tau aggregation in human neural stem cells","volume":"1852","author":"Chiang","year":"2025","journal-title":"Brain Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"13576","DOI":"10.1073\/pnas.0902714106","article-title":"Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer\u2019s disease","volume":"106","author":"Massaad","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"138252","DOI":"10.1016\/j.neulet.2025.138252","article-title":"Maternal exercise during pregnancy: Sex-specific impacts on offspring memory and maternal deprivation effects","volume":"856\u2013858","author":"Carrazoni","year":"2025","journal-title":"Neurosci. Lett."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Ogunro, O.B., Karigidi, M.E., Gyebi, G.A., Turkistani, A., and Almehmadi, A.H. (2025). Tangeretin offers neuroprotection against colchicine-induced memory impairment in Wistar rats by modulating the antioxidant milieu, inflammatory mediators and oxidative stress in the brain tissue. BMC Complement. Med. Ther., 25.","DOI":"10.1186\/s12906-025-04769-2"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"473706","DOI":"10.1155\/2013\/473706","article-title":"Evidence for prion-like mechanisms in several neurodegenerative diseases: Potential implications for immunotherapy","volume":"2013","author":"Marciniuk","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/nan.12592","article-title":"Invited Review: The role of prion-like mechanisms in neurodegenerative diseases","volume":"46","author":"Jaunmuktane","year":"2020","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Cabrera, A.C., Melo, E., Roth, D., Topp, A., Delobel, F., Stucki, C., Chen, C.Y., Jakob, P., Banfai, B., and Dunkley, T. (2017). HtrA1 activation is driven by an allosteric mechanism of inter-monomer communication. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-14208-z"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"6021","DOI":"10.1073\/pnas.0501823102","article-title":"Implications of the serine protease HtrA1 in amyloid precursor protein processing","volume":"102","author":"Grau","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s40478-022-01356-1","article-title":"The amyloid plaque proteome in early onset Alzheimer\u2019s disease and Down syndrome","volume":"10","author":"Drummond","year":"2022","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s12640-018-9895-1","article-title":"Clearance of Amyloid Beta and Tau in Alzheimer\u2019s Disease: From Mechanisms to Therapy","volume":"34","author":"Xin","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/S0002-9440(10)65234-0","article-title":"Mouse senile amyloid deposition is suppressed by adenovirus-mediated overexpression of amyloid-resistant apolipoprotein A-II","volume":"155","author":"Chiba","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/labinvest.3700559","article-title":"Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2c)","volume":"87","author":"Ge","year":"2007","journal-title":"Lab. Investig."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"855","DOI":"10.3233\/JAD-140111","article-title":"Apolipoprotein C-III is an amyloid-beta-binding protein and an early marker for Alzheimer\u2019s disease","volume":"41","author":"Shih","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Sacks, F.M., Furtado, J.D., and Jensen, M.K. (2022). Protein-based HDL subspecies: Rationale and association with cardiovascular disease, diabetes, stroke, and dementia. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1867.","DOI":"10.1016\/j.bbalip.2022.159182"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Song, Y., Shi, X., Gao, Z., Li, R., Tian, J., Cao, X., Yang, B., Zhao, S., and Yang, Y. (2023). Acupoint Catgut Embedding Improves Lipid Metabolism in Exercise-Induced Fatigue Rats via the PPAR Signaling Pathway. Animals, 13.","DOI":"10.3390\/ani13040558"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/clc.23104","article-title":"Aerobic exercise reduces triglycerides by targeting apolipoprotein C3 in patients with coronary heart disease","volume":"42","author":"Wang","year":"2019","journal-title":"Clin. Cardiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.coph.2021.07.011","article-title":"The pleiotropic roles of autophagy in Alzheimer\u2019s disease: From pathophysiology to therapy","volume":"60","author":"Festa","year":"2021","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.24272\/j.issn.2095-8137.2023.294","article-title":"Targeting autophagy in Alzheimer\u2019s disease: Animal models and mechanisms","volume":"44","author":"Zhang","year":"2023","journal-title":"Zool. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.stem.2013.01.009","article-title":"Modeling Alzheimer\u2019s disease with iPSCs reveals stress phenotypes associated with intracellular Abeta and differential drug responsiveness","volume":"12","author":"Kondo","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"957","DOI":"10.2353\/ajpath.2009.080480","article-title":"The E693Delta mutation in amyloid precursor protein increases intracellular accumulation of amyloid beta oligomers and causes endoplasmic reticulum stress-induced apoptosis in cultured cells","volume":"174","author":"Nishitsuji","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"16941","DOI":"10.1074\/jbc.M000937200","article-title":"Effects of incorporation of immunoglobulin G and complement component C1q on uptake and degradation of Alzheimer\u2019s disease amyloid fibrils by microglia","volume":"275","author":"Brazil","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Soto, I., Graham, L.C., Richter, H.J., Simeone, S.N., Radell, J.E., Grabowska, W., Funkhouser, W.K., Howell, M.C., and Howell, G.R. (2015). APOE Stabilization by Exercise Prevents Aging Neurovascular Dysfunction and Complement Induction. PLoS Biol., 13.","DOI":"10.1371\/journal.pbio.1002279"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1167\/iovs.18-25883","article-title":"Low-Intensity Exercise in Mice Is Sufficient to Protect Retinal Function During Light-Induced Retinal Degeneration","volume":"60","author":"Mees","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.nbd.2012.12.017","article-title":"Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury","volume":"54","author":"Piao","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"8354","DOI":"10.1523\/JNEUROSCI.0616-08.2008","article-title":"Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer\u2019s disease mice","volume":"28","author":"Hickman","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_122","first-page":"1","article-title":"The effects of exercise on complement system proteins in humans: A systematic scoping review","volume":"28","author":"Causer","year":"2022","journal-title":"Exerc. Immunol. Rev."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.bbrc.2014.10.066","article-title":"NDP52 associates with phosphorylated tau in brains of an Alzheimer disease mouse model","volume":"454","author":"Kim","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Zimbone, S., Di Rosa, M.C., Chiechio, S., and Giuffrida, M.L. (2023). Exploring the Role of Hsp60 in Alzheimer\u2019s Disease and Type 2 Diabetes: Suggestion for Common Drug Targeting. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512456"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Cui, K., Li, C., and Fang, G. (2023). Aerobic Exercise Delays Alzheimer\u2019s Disease by Regulating Mitochondrial Proteostasis in the Cerebral Cortex and Hippocampus. Life, 13.","DOI":"10.3390\/life13051204"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"25424823241307021","DOI":"10.1177\/25424823241307021","article-title":"Heat shock protein 70 in Alzheimer\u2019s disease and other dementias: A possible alternative therapeutic","volume":"9","year":"2025","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1016\/j.bbagen.2016.07.033","article-title":"Hsp90 directly interacts, in vitro, with amyloid structures and modulates their assembly and disassembly","volume":"1860","author":"Schirmer","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1152\/japplphysiol.01052.2018","article-title":"Role of heat shock proteins 70\/90 in exercise physiology and exercise immunology and their diagnostic potential in sports","volume":"126","author":"Kruger","year":"2019","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Uddin, M.S., Stachowiak, A., Mamun, A.A., Tzvetkov, N.T., Takeda, S., Atanasov, A.G., Bergantin, L.B., Abdel-Daim, M.M., and Stankiewicz, A.M. (2018). Autophagy and Alzheimer\u2019s Disease: From Molecular Mechanisms to Therapeutic Implications. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00004"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"25492","DOI":"10.1074\/jbc.M802072200","article-title":"Numb endocytic adapter proteins regulate the transport and processing of the amyloid precursor protein in an isoform-dependent manner: Implications for Alzheimer disease pathogenesis","volume":"283","author":"Kyriazis","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.ajhg.2024.02.005","article-title":"Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy","volume":"111","author":"Brugger","year":"2024","journal-title":"Am. J. Hum. Genet."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Fruhmann, G., Marchal, C., Vignaud, H., Verduyckt, M., Talarek, N., De Virgilio, C., Winderickx, J., and Cullin, C. (2018). The Impact of ESCRT on Abeta(1-42) Induced Membrane Lesions in a Yeast Model for Alzheimer\u2019s Disease. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00406"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"e14404","DOI":"10.1111\/acel.14404","article-title":"Overexpression of TECPR1 improved cognitive function of P301S-tau mice via activation of autophagy in the early and late process","volume":"24","author":"Li","year":"2025","journal-title":"Aging Cell"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/mrd.23083","article-title":"The eggstraordinary story of how life begins","volume":"86","author":"Parrington","year":"2019","journal-title":"Mol. Reprod. Dev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1126\/science.aad8373","article-title":"Complement and microglia mediate early synapse loss in Alzheimer mouse models","volume":"352","author":"Hong","year":"2016","journal-title":"Science"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Khoonsari, P.E., Haggmark, A., Lonnberg, M., Mikus, M., Kilander, L., Lannfelt, L., Bergquist, J., Ingelsson, M., Nilsson, P., and Kultima, K. (2016). Analysis of the Cerebrospinal Fluid Proteome in Alzheimer\u2019s Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150672"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Turturici, G., Sconzo, G., and Geraci, F. (2011). Hsp70 and its molecular role in nervous system diseases. Biochem. Res. Int., 2011.","DOI":"10.1155\/2011\/618127"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.2174\/1568026616666160413140741","article-title":"Neurodegeneration and the Heat Shock Protein 70 Machinery: Implications for Therapeutic Development","volume":"16","author":"Fontaine","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.2174\/1381612822666160518141437","article-title":"Alzheimer\u2019s Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy","volume":"22","author":"Bavisotto","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.2174\/1568026616666160413141350","article-title":"Stressing Out Hsp90 in Neurotoxic Proteinopathies","volume":"16","author":"Inda","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Lackie, R.E., Maciejewski, A., Ostapchenko, V.G., Marques-Lopes, J., Choy, W.Y., Duennwald, M.L., Prado, V.F., and Prado, M.A.M. (2017). The Hsp70\/Hsp90 Chaperone Machinery in Neurodegenerative Diseases. Front. Neurosci., 11.","DOI":"10.3389\/fnins.2017.00254"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Campanella, C., Pace, A., Caruso Bavisotto, C., Marzullo, P., Marino Gammazza, A., Buscemi, S., and Palumbo Piccionello, A. (2018). Heat Shock Proteins in Alzheimer\u2019s Disease: Role and Targeting. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092603"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"5238","DOI":"10.1158\/0008-5472.CAN-04-3804","article-title":"Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells","volume":"65","author":"Gastpar","year":"2005","journal-title":"Cancer Res."},{"key":"ref_144","first-page":"5267","article-title":"Suppression of Alzheimer\u2019s disease-related phenotypes by the heat shock protein 70 inducer, geranylgeranylacetone, in APP\/PS1 transgenic mice via the ERK\/p38 MAPK signaling pathway","volume":"14","author":"Sun","year":"2017","journal-title":"Exp. Ther. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9816\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:52:59Z","timestamp":1760107979000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,9]]},"references-count":144,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms26199816"],"URL":"https:\/\/doi.org\/10.3390\/ijms26199816","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,9]]}}}