{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:23:19Z","timestamp":1780633399358,"version":"3.54.1"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82073751"],"award-info":[{"award-number":["82073751"]}]},{"name":"National Natural Science Foundation of China","award":["32171246"],"award-info":[{"award-number":["32171246"]}]},{"name":"National Natural Science Foundation of China","award":["20S11904900"],"award-info":[{"award-number":["20S11904900"]}]},{"name":"National Natural Science Foundation of China","award":["21JC1403700"],"award-info":[{"award-number":["21JC1403700"]}]},{"DOI":"10.13039\/100012543","name":"Shanghai Science and Technology Commission Project","doi-asserted-by":"publisher","award":["82073751"],"award-info":[{"award-number":["82073751"]}],"id":[{"id":"10.13039\/100012543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012543","name":"Shanghai Science and Technology Commission Project","doi-asserted-by":"publisher","award":["32171246"],"award-info":[{"award-number":["32171246"]}],"id":[{"id":"10.13039\/100012543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012543","name":"Shanghai Science and Technology Commission Project","doi-asserted-by":"publisher","award":["20S11904900"],"award-info":[{"award-number":["20S11904900"]}],"id":[{"id":"10.13039\/100012543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012543","name":"Shanghai Science and Technology Commission Project","doi-asserted-by":"publisher","award":["21JC1403700"],"award-info":[{"award-number":["21JC1403700"]}],"id":[{"id":"10.13039\/100012543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyloidosis involves the deposition of misfolded proteins. Even though it is caused by different pathogenic mechanisms, in aggregate, it shares similar features. Here, we tested and confirmed a hypothesis that an amyloid antibody can be engineered by a few mutations to target a different species. Amyloid light chain (AL) and \u03b2-amyloid peptide (A\u03b2) are two therapeutic targets that are implicated in amyloid light chain amyloidosis and Alzheimer\u2019s disease, respectively. Though crenezumab, an anti-A\u03b2 antibody, is currently unsuccessful, we chose it as a model to computationally design and prepare crenezumab variants, aiming to discover a novel antibody with high affinity to AL fibrils and to establish a technology platform for repurposing amyloid monoclonal antibodies. We successfully re-engineered crenezumab to bind both A\u03b242 oligomers and AL fibrils with high binding affinities. It is capable of reversing A\u03b242-oligomers-induced cytotoxicity, decreasing the formation of AL fibrils, and alleviating AL-fibrils-induced cytotoxicity in vitro. Our research demonstrated that an amyloid antibody could be engineered by a few mutations to bind new amyloid sequences, providing an efficient way to reposition a therapeutic antibody to target different amyloid diseases.<\/jats:p>","DOI":"10.3390\/ijms25031593","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T04:57:07Z","timestamp":1706504227000},"page":"1593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Re-Engineering Therapeutic Anti-A\u03b2 Monoclonal Antibody to Target Amyloid Light Chain"],"prefix":"10.3390","volume":"25","author":[{"given":"Jingyi","family":"Bai","sequence":"first","affiliation":[{"name":"Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Li","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1498-0631","authenticated-orcid":false,"given":"Huifang","family":"Zong","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"Jecho Biopharmaceutical Institute, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1672-4455","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ke","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Han","sequence":"additional","affiliation":[{"name":"Jecho Biopharmaceutical Institute, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianrong","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-719X","authenticated-orcid":false,"given":"Buyong","family":"Ma","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6453-961X","authenticated-orcid":false,"given":"Baohong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6782-2023","authenticated-orcid":false,"given":"Jianwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"Jecho Biopharmaceutical Institute, Shanghai 200240, China"},{"name":"Jecho Laboratories, Inc., Frederick, MD 21704, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nrd3050","article-title":"Protein aggregation diseases: Pathogenicity and therapeutic perspectives","volume":"9","author":"Aguzzi","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.2215\/CJN.02740806","article-title":"Light-chain (AL) amyloidosis: Diagnosis and treatment","volume":"1","author":"Sanchorawala","year":"2006","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"eaax0914","DOI":"10.1126\/scitranslmed.aax0914","article-title":"Does protein aggregation drive postmitotic tissue degeneration?","volume":"13","author":"Kelly","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/S0140-6736(10)61349-9","article-title":"Alzheimer\u2019s disease","volume":"377","author":"Ballard","year":"2011","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.bbapap.2014.08.016","article-title":"Antibodies and protein misfolding: From structural research tools to therapeutic strategies","volume":"1844","author":"Messer","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jnc.12845","article-title":"Clearing the way for tau immunotherapy in Alzheimer\u2019s disease","volume":"132","author":"Herrmann","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/joim.12192","article-title":"Pathways to Alzheimer\u2019s disease","volume":"275","author":"Hardy","year":"2014","journal-title":"J. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13195-018-0424-5","article-title":"Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild-to-moderate Alzheimer\u2019s disease (BLAZE)","volume":"10","author":"Salloway","year":"2018","journal-title":"Alzheimers Res. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9677","DOI":"10.1523\/JNEUROSCI.4742-11.2012","article-title":"An effector-reduced anti-\u03b2-amyloid (A\u03b2) antibody with unique a\u03b2 binding properties promotes neuroprotection and glial engulfment of A\u03b2","volume":"32","author":"Adolfsson","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1093\/ckj\/sfu117","article-title":"The clinical features and outcomes of systemic AL amyloidosis: A cohort of 231 Chinese patients","volume":"8","author":"Huang","year":"2015","journal-title":"Clin. Kidney J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000444287","article-title":"The Clinical Presentation and Management of Systemic Light-Chain Amyloidosis in China","volume":"2","author":"Huang","year":"2016","journal-title":"Kidney Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.clml.2015.11.001","article-title":"Clinical Characteristics and Treatment Outcome of Chinese Patients With Systemic Amyloid Light-Chain Amyloidosis: A Retrospective Single-Center Analysis","volume":"16","author":"Zhao","year":"2016","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_13","first-page":"45","article-title":"Primary systemic amyloidosis: Clinical and laboratory features in 474 cases","volume":"32","author":"Kyle","year":"1995","journal-title":"Semin. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41572-018-0034-3","article-title":"Systemic immunoglobulin light chain amyloidosis","volume":"4","author":"Merlini","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1056\/NEJMra023144","article-title":"Molecular mechanisms of amyloidosis","volume":"349","author":"Merlini","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E506","DOI":"10.1002\/ajh.24563","article-title":"Organ response in patients with AL amyloidosis treated with NEOD001, an amyloid-directed monoclonal antibody","volume":"91","author":"Gertz","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/S0002-9440(10)64639-1","article-title":"Antibody-mediated resolution of light chain-associated amyloid deposits","volume":"157","author":"Hrncic","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1021\/bi0616605","article-title":"Localization of a conformational epitope common to non-native and fibrillar immunoglobulin light chains","volume":"46","author":"Allen","year":"2007","journal-title":"Biochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1182\/blood-2010-03-273797","article-title":"Radioimmunodetection of amyloid deposits in patients with AL amyloidosis","volume":"116","author":"Wall","year":"2010","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1182\/blood.2020009039","article-title":"Phase 1a\/b study of monoclonal antibody CAEL-101 (11-1F4) in patients with AL amyloidosis","volume":"138","author":"Edwards","year":"2021","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"27513","DOI":"10.1074\/jbc.M114.585638","article-title":"Formation of amyloid fibers by monomeric light chain variable domains","volume":"289","author":"Brumshtein","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1016\/j.bbadis.2017.12.009","article-title":"Structure and energetic basis of overrepresented \u03bb light chain in systemic light chain amyloidosis patients","volume":"1864","author":"Zhao","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12104-016-9718-3","article-title":"Solid-state NMR chemical shift assignments for AL-09 V(L) immunoglobulin light chain fibrils","volume":"11","author":"Piehl","year":"2017","journal-title":"Biomol. NMR Assign."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/s41467-019-09032-0","article-title":"Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis","volume":"10","author":"Radamaker","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1038\/s41467-019-09133-w","article-title":"Cryo-EM structure of cardiac amyloid fibrils from an immunoglobulin light chain AL amyloidosis patient","volume":"10","author":"Swuec","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/s41467-021-21126-2","article-title":"Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis","volume":"12","author":"Radamaker","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6434","DOI":"10.1038\/s41467-021-26553-9","article-title":"Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM","volume":"12","author":"Radamaker","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1073\/pnas.022662599","article-title":"Conformational Abs recognizing a generic amyloid fibril epitope","volume":"99","author":"Wetzel","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"393","DOI":"10.2174\/1567205014666170116152622","article-title":"Conformation as the Therapeutic Target for Neurodegenerative Diseases","volume":"14","author":"Krishnan","year":"2017","journal-title":"Curr. Alzheimer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.3233\/JAD-150882","article-title":"The Anti-Prion Antibody 15B3 Detects Toxic Amyloid-\u03b2 Oligomers","volume":"53","author":"Stravalaci","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd.2018.168","article-title":"Drug repurposing: Progress, challenges and recommendations","volume":"18","author":"Pushpakom","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1016\/j.bbagen.2016.05.040","article-title":"Conformational selection in amyloid-based immunotherapy: Survey of crystal structures of antibody-amyloid complexes","volume":"1860","author":"Ma","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"14101","DOI":"10.1021\/bi991131j","article-title":"Thermodynamic instability of human lambda 6 light chains: Correlation with fibrillogenicity","volume":"38","author":"Wall","year":"1999","journal-title":"Biochemistry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1093\/nar\/gkg520","article-title":"SWISS-MODEL: An automated protein homology-modeling server","volume":"31","author":"Schwede","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"20634","DOI":"10.1039\/D1CP01825F","article-title":"Computational investigation of the binding of a designed peptide to \u03bb light chain amyloid fibril","volume":"23","author":"Wang","year":"2021","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/nprot.2010.32","article-title":"The HADDOCK web server for data-driven biomolecular docking","volume":"5","author":"Bonvin","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1093\/bioinformatics\/btm124","article-title":"PROTMAP2D: Visualization, comparison and analysis of 2D maps of protein structure","volume":"23","author":"Pietal","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2693","DOI":"10.1002\/jmr.2693","article-title":"Local and global anatomy of antibody-protein antigen recognition","volume":"31","author":"Wang","year":"2018","journal-title":"J. Mol. Recognit."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"39374","DOI":"10.1038\/srep39374","article-title":"Structure of Crenezumab Complex with A\u03b2 Shows Loss of \u03b2-Hairpin","volume":"6","author":"Ultsch","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/978-1-4939-8648-4_24","article-title":"The Use of Somatic Hypermutation for the Affinity Maturation of Therapeutic Antibodies","volume":"1827","author":"Bowers","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.bej.2018.06.003","article-title":"Understanding and overcoming trade-offs between antibody affinity, specificity, stability and solubility","volume":"137","author":"Rabia","year":"2018","journal-title":"Biochem. Eng. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/jb\/mvy016","article-title":"Impact in stability during sequential CDR grafting to construct camelid VHH antibodies against zinc oxide and gold","volume":"164","author":"Saito","year":"2018","journal-title":"J. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10879","DOI":"10.1073\/pnas.1202866109","article-title":"General strategy for the generation of human antibody variable domains with increased aggregation resistance","volume":"109","author":"Dudgeon","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/protein\/gzt058","article-title":"Optimal charged mutations in the complementarity-determining regions that prevent domain antibody aggregation are dependent on the antibody scaffold","volume":"27","author":"Perchiacca","year":"2014","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6448","DOI":"10.1073\/pnas.95.11.6448","article-title":"Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins","volume":"95","author":"Lambert","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1002\/1531-8249(199912)46:6<860::AID-ANA8>3.0.CO;2-M","article-title":"Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer\u2019s disease","volume":"46","author":"McLean","year":"1999","journal-title":"Ann. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1006\/exnr.1999.7085","article-title":"The levels of soluble versus insoluble brain Abeta distinguish Alzheimer\u2019s disease from normal and pathologic aging","volume":"158","author":"Wang","year":"1999","journal-title":"Exp. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.bbapap.2016.01.009","article-title":"Probing the role of \u03bb6 immunoglobulin light chain dimerization in amyloid formation","volume":"1864","author":"Wolwertz","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"McWilliams-Koeppen, H.P., Foster, J.S., Hackenbrack, N., Ramirez-Alvarado, M., Donohoe, D., Williams, A., Macy, S., Wooliver, C., Wortham, D., and Morrell-Falvey, J. (2015). Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137716"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.1073\/pnas.0912263107","article-title":"Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38\u03b1 MAPK pathway","volume":"107","author":"Shi","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","first-page":"1115","article-title":"Altered diastolic function and aortic stiffness in Alzheimer\u2019s disease","volume":"9","author":"Varlibas","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.tibs.2004.08.009","article-title":"Conformation-dependent antibodies target diseases of protein misfolding","volume":"29","author":"Glabe","year":"2004","journal-title":"Trends Biochem. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3233\/JAD-150696","article-title":"The Anti-Amyloid-\u03b2 Monoclonal Antibody 4G8 Recognizes a Generic Sequence-Independent Epitope Associated with \u03b1-Synuclein and Islet Amyloid Polypeptide Amyloid Fibrils","volume":"50","author":"Hatami","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/med.21440","article-title":"Bridging Type 2 Diabetes and Alzheimer\u2019s Disease: Assembling the Puzzle Pieces in the Quest for the Molecules with Therapeutic and Preventive Potential","volume":"38","author":"Rauter","year":"2018","journal-title":"Med. Res. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"18325","DOI":"10.1074\/jbc.M117.801514","article-title":"Mechanisms of recognition of amyloid-\u03b2 (A\u03b2) monomer, oligomer, and fibril by homologous antibodies","volume":"292","author":"Zhao","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Chaudhury, S., Berrondo, M., Weitzner, B.D., Muthu, P., Bergman, H., and Gray, J.J. (2011). Benchmarking and analysis of protein docking performance in Rosetta v3.2. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022477"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1006\/jcph.1999.6201","article-title":"NAMD2: Greater scalability for parallel molecular dynamics","volume":"151","author":"Skeel","year":"1999","journal-title":"J. Comput. Phys."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1021\/jp973084f","article-title":"All-atom empirical potential for molecular modeling and dynamics studies of proteins","volume":"102","author":"MacKerell","year":"1998","journal-title":"J. Phys. Chem. B"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1002\/jcc.10272","article-title":"New analytic approximation to the standard molecular volume definition and its application to generalized Born calculations","volume":"24","author":"Lee","year":"2003","journal-title":"J. Comput. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1042\/BJ20101712","article-title":"An anti-A\u03b2 (amyloid \u03b2) single-chain variable fragment prevents amyloid fibril formation and cytotoxicity by withdrawing A\u03b2 oligomers from the amyloid pathway","volume":"437","author":"Villegas","year":"2011","journal-title":"Biochem. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1110\/ps.8.3.509","article-title":"Physicochemical consequences of amino acid variations that contribute to fibril formation by immunoglobulin light chains","volume":"8","author":"Raffen","year":"1999","journal-title":"Protein Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1593\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:50:20Z","timestamp":1760104220000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,27]]},"references-count":61,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25031593"],"URL":"https:\/\/doi.org\/10.3390\/ijms25031593","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,27]]}}}