Recombinant Antibody Fragments for Neurological Disorders: An Update
- Autores: Manoutcharian K.1, Gevorkian G.1
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Afiliações:
- Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), CDMX
- Edição: Volume 22, Nº 13 (2024)
- Páginas: 2157-2167
- Seção: Neurology
- URL: https://rjraap.com/1570-159X/article/view/644476
- DOI: https://doi.org/10.2174/1570159X21666230830142554
- ID: 644476
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Resumo
:Recombinant antibody fragments are promising alternatives to full-length immunoglobulins, creating big opportunities for the pharmaceutical industry. Nowadays, antibody fragments such as antigen-binding fragments (Fab), single-chain fragment variable (scFv), single-domain antibodies (sdAbs), and bispecific antibodies (bsAbs) are being evaluated as diagnostics or therapeutics in preclinical models and in clinical trials. Immunotherapy approaches, including passive transfer of protective antibodies, have shown therapeutic efficacy in several animal models of Alzheimer´s disease (AD), Parkinson´s disease (PD), frontotemporal dementia (FTD), Huntington´s disease (HD), transmissible spongiform encephalopathies (TSEs) and multiple sclerosis (MS). There are various antibodies approved by the Food and Drug Administration (FDA) for treating multiple sclerosis and two amyloid beta-specific humanized antibodies, Aducanumab and Lecanemab, for AD. Our previous review summarized data on recombinant antibodies evaluated in pre-clinical models for immunotherapy of neurodegenerative diseases. Here, we explore recent studies in this fascinating research field, give an update on new preventive and therapeutic applications of recombinant antibody fragments for neurological disorders and discuss the potential of antibody fragments for developing novel approaches for crossing the blood-brain barrier (BBB) and targeting cells and molecules of interest in the brain.
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Sobre autores
Karen Manoutcharian
Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), CDMX
Email: info@benthamscience.net
Goar Gevorkian
Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), CDMX
Autor responsável pela correspondência
Email: info@benthamscience.net
Bibliografia
- Bird, R.; Walker, B.W. Single chain antibody variable regions. Trends Biotechnol., 1991, 9(1), 132-137. doi: 10.1016/0167-7799(91)90044-I PMID: 1367550
- Morrison, S.L. In vitro antibodies: Strategies for production and application. Annu. Rev. Immunol., 1992, 10(1), 239-265. doi: 10.1146/annurev.iy.10.040192.001323 PMID: 1590987
- Plückthun, A.; Pack, P. New protein engineering approaches to multivalent and bispecific antibody fragments. Immunotechnology, 1997, 3(2), 83-105. doi: 10.1016/S1380-2933(97)00067-5 PMID: 9237094
- Ma, H.; OKennedy, R. Recombinant antibody fragment production. Methods, 2017, 116, 23-33. doi: 10.1016/j.ymeth.2016.11.008 PMID: 27871972
- Manoutcharian, K.; Perez-Garmendia, R.; Gevorkian, G. Recombinant antibody fragments for neurodegenerative diseases. Curr. Neuropharmacol., 2017, 15(5), 779-788. doi: 10.2174/1570159X01666160930121647 PMID: 27697033
- Pietersz, G.A.; Wang, X.; Yap, M.L.; Lim, B.; Peter, K. Therapeutic targeting in nanomedicine: The future lies in recombinant antibodies. Nanomedicine, 2017, 12(15), 1873-1889. doi: 10.2217/nnm-2017-0043 PMID: 28703636
- Bélanger, K.; Iqbal, U.; Tanha, J.; MacKenzie, R.; Moreno, M.; Stanimirovic, D. Single-domain antibodies as therapeutic and imaging agents for the treatment of CNS diseases. Antibodies, 2019, 8(2), 27. doi: 10.3390/antib8020027 PMID: 31544833
- Bates, A.; Power, C.A. David vs. Goliath: The structure, function, and clinical prospects of antibody fragments. Antibodies, 2019, 8(2), 28. doi: 10.3390/antib8020028 PMID: 31544834
- Salvador, J.P.; Vilaplana, L.; Marco, M.P. Nanobody: Outstanding features for diagnostic and therapeutic applications. Anal. Bioanal. Chem., 2019, 411(9), 1703-1713. doi: 10.1007/s00216-019-01633-4 PMID: 30734854
- Pothin, E.; Lesuisse, D.; Lafaye, P. Brain delivery of single-domain antibodies: A focus on VHH and VNAR. Pharmaceutics, 2020, 12(10), 937. doi: 10.3390/pharmaceutics12100937 PMID: 33007904
- Gao, Y.; Zhu, J.; Lu, H. Single domain antibody-based vectors in the delivery of biologics across the bloodbrain barrier: A review. Drug Deliv. Transl. Res., 2021, 11(5), 1818-1828. doi: 10.1007/s13346-020-00873-7 PMID: 33155179
- Roth, K.D.R.; Wenzel, E.V.; Ruschig, M.; Steinke, S.; Langreder, N.; Heine, P.A.; Schneider, K.T.; Ballmann, R.; Fühner, V.; Kuhn, P.; Schirrmann, T.; Frenzel, A.; Dübel, S.; Schubert, M.; Moreira, G.M.S.G.; Bertoglio, F.; Russo, G.; Hust, M. Developing recombinant antibodies by phage display against infectious diseases and toxins for diagnostics and therapy. Front. Cell. Infect. Microbiol., 2021, 11, 697876. doi: 10.3389/fcimb.2021.697876 PMID: 34307196
- Ruiz-López, E.; Schuhmacher, A.J. Transportation of single-domain antibodies through the bloodbrain barrier. Biomolecules, 2021, 11(8), 1131. doi: 10.3390/biom11081131 PMID: 34439797
- Naidoo, D.B.; Chuturgoon, A.A. The potential of nanobodies for COVID-19 diagnostics and therapeutics. Mol. Diagn. Ther., 2023, 27(2), 193-226. doi: 10.1007/s40291-022-00634-x PMID: 36656511
- Fuller, J.P.; Stavenhagen, J.B.; Teeling, J.L. New roles for Fc receptors in neurodegeneration-the impact on Immunotherapy for Alzheimers Disease. Front. Neurosci., 2014, 8, 235. doi: 10.3389/fnins.2014.00235 PMID: 25191216
- Sun, X.; Yu, X.; Zhu, J.; Li, L.; Zhang, L.; Huang, Y.; Liu, D.; Ji, M.; Sun, X.; Zhang, L.; Zhou, W.; Zhang, D.; Jiao, J.; Liu, R. Fc effector of anti-Aβ antibody induces synapse loss and cognitive deficits in Alzheimers disease-like mouse model. Signal Transduct. Target. Ther., 2023, 8(1), 30. doi: 10.1038/s41392-022-01273-8 PMID: 36693826
- Huang, L.; Su, X.; Federoff, H. Single-chain fragment variable passive immunotherapies for neurodegenerative diseases. Int. J. Mol. Sci., 2013, 14(9), 19109-19127. doi: 10.3390/ijms140919109 PMID: 24048248
- Lulu, S.; Waubant, E. Humoral-targeted immunotherapies in multiple sclerosis. Neurotherapeutics, 2013, 10(1), 34-43. doi: 10.1007/s13311-012-0164-3 PMID: 23208729
- Cardinale, A.; Merlo, D.; Giunchedi, P.; Biocca, S. Therapeutic application of intrabodies against age-related neurodegenerative disorders. Curr. Pharm. Des., 2014, 20(38), 6028-6036. doi: 10.2174/1381612820666140314121444 PMID: 24641233
- Wootla, B.; Watzlawik, J.O.; Stavropoulos, N.; Wittenberg, N.J.; Dasari, H.; Abdelrahim, M.A.; Henley, J.R.; Oh, S.H.; Warrington, A.E.; Rodriguez, M. Recent advances in monoclonal antibody therapies for multiple sclerosis. Expert Opin. Biol. Ther., 2016, 16(6), 827-839. doi: 10.1517/14712598.2016.1158809 PMID: 26914737
- Frontzek, K.; Aguzzi, A. Recent developments in antibody therapeutics against prion disease. Emerg. Top. Life Sci., 2020, 4(2), 169-173. doi: 10.1042/ETLS20200002 PMID: 32633322
- Jamwal, S.; Elsworth, J.D.; Rahi, V.; Kumar, P. Gene therapy and immunotherapy as promising strategies to combat Huntingtons disease-associated neurodegeneration: emphasis on recent updates and future perspectives. Expert Rev. Neurother., 2020, 20(11), 1123-1141. doi: 10.1080/14737175.2020.1801424 PMID: 32720531
- Panza, F.; Lozupone, M.; Seripa, D.; Daniele, A.; Watling, M.; Giannelli, G.; Imbimbo, B.P. Development of disease-modifying drugs for frontotemporal dementia spectrum disorders. Nat. Rev. Neurol., 2020, 16(4), 213-228. doi: 10.1038/s41582-020-0330-x PMID: 32203398
- Haddad, H.W.; Malone, G.W.; Comardelle, N.J.; Degueure, A.E.; Poliwoda, S.; Kaye, R.J.; Murnane, K.S.; Kaye, A.M.; Kaye, A.D. Aduhelm, a novel anti-amyloid monoclonal antibody, for the treatment of Alzheimers Disease: A comprehensive review. Health Psychol. Res., 2022, 10(2), 37023. doi: 10.52965/001c.37023 PMID: 35910244
- Menon, S.; Armstrong, S.; Hamzeh, A.; Visanji, N.P.; Sardi, S.P.; Tandon, A. Alpha-synuclein targeting therapeutics for Parkinsons Disease and related synucleinopathies. Front. Neurol., 2022, 13, 852003. doi: 10.3389/fneur.2022.852003 PMID: 35614915
- Bateman, R.J.; Cummings, J.; Schobel, S.; Salloway, S.; Vellas, B.; Boada, M.; Black, S.E.; Blennow, K.; Fontoura, P.; Klein, G.; Assunção, S.S.; Smith, J.; Doody, R.S. Gantenerumab: an anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimers disease. Alzheimers Res. Ther., 2022, 14(1), 178. doi: 10.1186/s13195-022-01110-8 PMID: 36447240
- De Genst, E.; Messer, A.; Dobson, C.M. Antibodies and protein misfolding: From structural research tools to therapeutic strategies. Biochim. Biophys. Acta. Proteins Proteomics, 2014, 1844(11), 1907-1919. doi: 10.1016/j.bbapap.2014.08.016 PMID: 25194824
- Valera, E.; Spencer, B.; Masliah, E. Immunotherapeutic approaches targeting amyloid-β, α-synuclein, and tau for the treatment of neurodegenerative disorders. Neurotherapeutics, 2016, 13(1), 179-189. doi: 10.1007/s13311-015-0397-z PMID: 26494242
- Chia, K.Y.; Ng, K.Y.; Koh, R.Y.; Chye, S.M. Single-chain Fv antibodies for targeting neurodegenerative diseases. CNS Neurol. Disord. Drug Targets, 2018, 17(9), 671-679. doi: 10.2174/1871527317666180315161626 PMID: 29546836
- Messer, A.; Butler, D.C. Optimizing intracellular antibodies (intrabodies/nanobodies) to treat neurodegenerative disorders. Neurobiol. Dis., 2020, 134, 104619. doi: 10.1016/j.nbd.2019.104619 PMID: 31669671
- Benn, J.A.; Mukadam, A.S.; McEwan, W.A. Targeted protein degradation using intracellular antibodies and its application to neurodegenerative disease. Semin. Cell Dev. Biol., 2022, 126, 138-149. doi: 10.1016/j.semcdb.2021.09.012 PMID: 34654628
- Iqbal, K.; Grundke-Iqbal, I. Alzheimers disease, a multifactorial disorder seeking multitherapies. Alzheimers Dement., 2010, 6(5), 420-424. doi: 10.1016/j.jalz.2010.04.006 PMID: 20813343
- Gong, C.X.; Liu, F.; Iqbal, K. Multifactorial hypothesis and multi-targets for Alzheimers Disease. J. Alzheimers Dis., 2018, 64(s1), S107-S117. doi: 10.3233/JAD-179921 PMID: 29562523
- Boyd, R.J.; Avramopoulos, D.; Jantzie, L.L.; McCallion, A.S. Neuroinflammation represents a common theme amongst genetic and environmental risk factors for Alzheimer and Parkinson diseases. J. Neuroinflammation, 2022, 19(1), 223. doi: 10.1186/s12974-022-02584-x PMID: 36076238
- Penke, B.; Szűcs, M.; Bogár, F. New pathways identify novel drug targets for the prevention and treatment of Alzheimers Disease. Int. J. Mol. Sci., 2023, 24(6), 5383. doi: 10.3390/ijms24065383 PMID: 36982456
- Selkoe, D.J. Altered structural proteins in plaques and tangles: What do they tell us about the biology of Alzheimers disease? Neurobiol. Aging, 1986, 7(6), 425-432. doi: 10.1016/0197-4580(86)90055-2 PMID: 3104810
- LaFerla, F.M.; Green, K.N.; Oddo, S. Intracellular amyloid-β in Alzheimers disease. Nat. Rev. Neurosci., 2007, 8(7), 499-509. doi: 10.1038/nrn2168 PMID: 17551515
- Montoliu-Gaya, L.; Murciano-Calles, J.; Martinez, J.C.; Villegas, S. Towards the improvement in stability of an anti-Aβ single-chain variable fragment, scFv-h3D6, as a way to enhance its therapeutic potential. Amyloid, 2017, 24(3), 167-175. doi: 10.1080/13506129.2017.1348347 PMID: 28699800
- Montoliu-Gaya, L.; Mulder, S.D.; Herrebout, M.A.C.; Baayen, J.C.; Villegas, S.; Veerhuis, R. Aβ-oligomer uptake and the resulting inflammatory response in adult human astrocytes are precluded by an anti-Aβ single chain variable fragment in combination with an apoE mimetic peptide. Mol. Cell. Neurosci., 2018, 89, 49-59. doi: 10.1016/j.mcn.2018.03.015 PMID: 29625180
- Söllvander, S.; Nikitidou, E.; Brolin, R.; Söderberg, L.; Sehlin, D.; Lannfelt, L.; Erlandsson, A. Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons. Mol. Neurodegener., 2016, 11(1), 38. doi: 10.1186/s13024-016-0098-z PMID: 27176225
- Montoliu-Gaya, L.; Esquerda-Canals, G.; Bronsoms, S.; Villegas, S. Production of an anti-Aβ antibody fragment in Pichia pastoris and in vitro and in vivo validation of its therapeutic effect. PLoS One, 2017, 12(8), e0181480. doi: 10.1371/journal.pone.0181480 PMID: 28771492
- Esquerda-Canals, G.; Martí-Clúa, J.; Villegas, S. Pharmacokinetic parameters and mechanism of action of an efficient anti-Aβ single chain antibody fragment. PLoS One, 2019, 14(5), e0217793. doi: 10.1371/journal.pone.0217793 PMID: 31150495
- Esquerda-Canals, G.; Roda, A.R.; Martí-Clúa, J.; Montoliu-Gaya, L.; Rivera-Hernández, G.; Villegas, S. Treatment with scFv-h3D6 prevented neuronal loss and improved spatial memory in young 3xTg-AD mice by reducing the intracellular amyloid-β burden. J. Alzheimers Dis., 2019, 70(4), 1069-1091. doi: 10.3233/JAD-190484 PMID: 31306135
- Güell-Bosch, J.; Lope-Piedrafita, S.; Esquerda-Canals, G.; Montoliu-Gaya, L.; Villegas, S. Progression of Alzheimers disease and effect of scFv-h3D6 immunotherapy in the 3xTg-AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy. NMR Biomed., 2020, 33(5), e4263. doi: 10.1002/nbm.4263 PMID: 32067292
- Roda, A.R.; Montoliu-Gaya, L.; Serra-Mir, G.; Villegas, S. Both amyloid-β peptide and tau protein are affected by an anti-amyloid-β antibody fragment in elderly 3xTg-AD mice. Int. J. Mol. Sci., 2020, 21(18), 6630. doi: 10.3390/ijms21186630 PMID: 32927795
- Williams, S.M.; Schulz, P.; Rosenberry, T.L.; Caselli, R.J.; Sierks, M.R. Blood-based oligomeric and other protein variant biomarkers to facilitate pre-symptomatic diagnosis and staging of Alzheimers disease. J. Alzheimers Dis., 2017, 58(1), 23-35. doi: 10.3233/JAD-161116 PMID: 28372328
- Cho, H.J.; Schulz, P.; Venkataraman, L.; Caselli, R.J.; Sierks, M.R. Sex-specific multiparameter blood test for the early diagnosis of Alzheimers Disease. Int. J. Mol. Sci., 2022, 23(24), 15670. doi: 10.3390/ijms232415670 PMID: 36555310
- Habiba, U.; Descallar, J.; Kreilaus, F.; Adhikari, U.K.; Kumar, S.; Morley, J.W.; Bui, B.V.; Koronyo-Hamaoui, M.; Tayebi, M. Detection of retinal and blood Aβ oligomers with nanobodies. Alzheimers Dement., 2021, 13(1), e12193. doi: 10.1002/dad2.12193 PMID: 33977118
- Li, T.; Vandesquille, M.; Koukouli, F.; Dudeffant, C.; Youssef, I.; Lenormand, P.; Ganneau, C.; Maskos, U.; Czech, C.; Grueninger, F.; Duyckaerts, C.; Dhenain, M.; Bay, S.; Delatour, B.; Lafaye, P. Camelid single-domain antibodies: A versatile tool for in vivo imaging of extracellular and intracellular brain targets. J. Control. Release, 2016, 243, 1-10. doi: 10.1016/j.jconrel.2016.09.019 PMID: 27671875
- Vandesquille, M.; Li, T.; Po, C.; Ganneau, C.; Lenormand, P.; Dudeffant, C.; Czech, C.; Grueninger, F.; Duyckaerts, C.; Delatour, B.; Dhenain, M.; Lafaye, P.; Bay, S. Chemically-defined camelid antibody bioconjugate for the magnetic resonance imaging of Alzheimers disease. MAbs, 2017, 9(6), 1016-1027. doi: 10.1080/19420862.2017.1342914 PMID: 28657418
- Sebollela, A.; Cline, E.N.; Popova, I.; Luo, K.; Sun, X.; Ahn, J.; Barcelos, M.A.; Bezerra, V.N.; Lyra e Silva, N.M.; Patel, J.; Pinheiro, N.R.; Qin, L.A.; Kamel, J.M.; Weng, A.; DiNunno, N.; Bebenek, A.M.; Velasco, P.T.; Viola, K.L.; Lacor, P.N.; Ferreira, S.T.; Klein, W.L. A human scFv antibody that targets and neutralizes high molecular weight pathogenic amyloid‐β oligomers. J. Neurochem., 2017, 142(6), 934-947. doi: 10.1111/jnc.14118 PMID: 28670737
- Cline, E.N.; Bicca, M.A.; Viola, K.L.; Klein, W.L. The amyloid-β oligomer hypothesis: Beginning of the third decade. J. Alzheimers Dis., 2018, 64(S1), S567-S610. doi: 10.3233/JAD-179941 PMID: 29843241
- Selles, M.C.; Fortuna, J.T.S.; Cercato, M.C.; Santos, L.E.; Domett, L.; Bitencourt, A.L.B.; Carraro, M.F.; Souza, A.S.; Janickova, H.; Azevedo, C.V.; Campos, H.C.; de Souza, J.M.; Alves-Leon, S.; Prado, V.F.; Prado, M.A.M.; Epstein, A.L.; Salvetti, A.; Longo, B.M.; Arancio, O.; Klein, W.L.; Sebollela, A.; De Felice, F.G.; Jerusalinsky, D.A.; Ferreira, S.T. AAV-mediated neuronal expression of an scFv antibody selective for Aβ oligomers protects synapses and rescues memory in Alzheimer models. Mol. Ther., 2023, 31(2), 409-419. doi: 10.1016/j.ymthe.2022.11.002 PMID: 36369741
- Hu, M.; Zhang, J.; Yang, J.; Cao, Y.; Qi, J. A novel scFv Anti-Aβ antibody reduces pathological impairments in APP/PS1 transgenic mice via modulation of inflammatory cytokines and aβ-related enzymes. J. Mol. Neurosci., 2018, 66(1), 1-9. doi: 10.1007/s12031-018-1139-6 PMID: 30062438
- Vitale, F.; Giliberto, L.; Ruiz, S.; Steslow, K.; Marambaud, P.; dAbramo, C. Anti-tau conformational scFv MC1 antibody efficiently reduces pathological tau species in adult JNPL3 mice. Acta Neuropathol. Commun., 2018, 6(1), 82. doi: 10.1186/s40478-018-0585-2 PMID: 30134961
- Vitale, F.; Ortolan, J.; Volpe, B.T.; Marambaud, P.; Giliberto, L.; dAbramo, C. Intramuscular injection of vectorized-scFvMC1 reduces pathological tau in two different tau transgenic models. Acta Neuropathol. Commun., 2020, 8(1), 126. doi: 10.1186/s40478-020-01003-7 PMID: 32762731
- Zhang, Y.; Qian, L.; Kuang, Y.; Liu, J.; Wang, D.; Xie, W.; Zhang, L.; Fu, L. An adeno-associated virus-mediated immunotherapy for Alzheimers disease. Mol. Immunol., 2022, 144, 26-34. doi: 10.1016/j.molimm.2022.02.006 PMID: 35172225
- Danis, C.; Dupré, E.; Zejneli, O.; Caillierez, R.; Arrial, A.; Bégard, S.; Mortelecque, J.; Eddarkaoui, S.; Loyens, A.; Cantrelle, F.X.; Hanoulle, X.; Rain, J.C.; Colin, M.; Buée, L.; Landrieu, I. Inhibition of Tau seeding by targeting Tau nucleation core within neurons with a single domain antibody fragment. Mol. Ther., 2022, 30(4), 1484-1499. doi: 10.1016/j.ymthe.2022.01.009 PMID: 35007758
- Guo, T.; Noble, W.; Hanger, D.P. Roles of tau protein in health and disease. Acta Neuropathol., 2017, 133(5), 665-704. doi: 10.1007/s00401-017-1707-9 PMID: 28386764
- Spencer, B.; Brüschweiler, S.; Sealey-Cardona, M.; Rockenstein, E.; Adame, A.; Florio, J.; Mante, M.; Trinh, I.; Rissman, R.A.; Konrat, R.; Masliah, E. Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders. Acta Neuropathol., 2018, 136(1), 69-87. doi: 10.1007/s00401-018-1869-0 PMID: 29934874
- Panza, F.; Lozupone, M.; Solfrizzi, V.; Sardone, R.; Piccininni, C.; Dibello, V.; Stallone, R.; Giannelli, G.; Bellomo, A.; Greco, A.; Daniele, A.; Seripa, D.; Logroscino, G.; Imbimbo, B.P. BACE inhibitors in clinical development for the treatment of Alzheimers disease. Expert Rev. Neurother., 2018, 18(11), 847-857. doi: 10.1080/14737175.2018.1531706 PMID: 30277096
- Marino, M.; Zhou, L.; Rincon, M.Y.; Callaerts-Vegh, Z.; Verhaert, J.; Wahis, J.; Creemers, E.; Yshii, L.; Wierda, K.; Saito, T.; Marneffe, C.; Voytyuk, I.; Wouters, Y.; Dewilde, M.; Duqué, S.I.; Vincke, C.; Levites, Y.; Golde, T.E.; Saido, T.C.; Muyldermans, S.; Liston, A.; De Strooper, B.; Holt, M.G. AAV‐mediated delivery of an anti‐BACE1 VHH alleviates pathology in an Alzheimers disease model. EMBO Mol. Med., 2022, 14(4), e09824. doi: 10.15252/emmm.201809824 PMID: 35352880
- Fahrenholz, F. Alpha-secretase as a therapeutic target. Curr. Alzheimer Res., 2007, 4(4), 412-417. doi: 10.2174/156720507781788837 PMID: 17908044
- Lichtenthaler, S.F.; Tschirner, S.K.; Steiner, H. Secretases in Alzheimers disease: Novel insights into proteolysis of APP and TREM2. Curr. Opin. Neurobiol., 2022, 72, 101-110. doi: 10.1016/j.conb.2021.09.003 PMID: 34689040
- He, P.; Xin, W.; Schulz, P.; Sierks, M.R. Bispecific antibody fragment targeting app and inducing α-site cleavage restores neuronal health in an alzheimers mouse model. Mol. Neurobiol., 2019, 56(11), 7420-7432. doi: 10.1007/s12035-019-1597-z PMID: 31041656
- Zhao, L.; Meng, F.; Li, Y.; Liu, S.; Xu, M.; Chu, F.; Li, C.; Yang, X.; Luo, L. Multivalent nanobody conjugate with rigid, reactive oxygen species scavenging scaffold for multi‐target therapy of Alzheimers Disease. Adv. Mater., 2023, 35(17), 2210879. doi: 10.1002/adma.202210879 PMID: 36786375
- Saleh, M.; Markovic, M.; Olson, K.E.; Gendelman, H.E.; Mosley, R.L. Therapeutic strategies for immune transformation in parkinsons disease. J. Parkinsons Dis., 2022, 12(s1), S201-S222. doi: 10.3233/JPD-223278 PMID: 35871362
- Massey, A.; Boag, M.; Magnier, A.; Bispo, D.; Khoo, T.; Pountney, D. Glymphatic system dysfunction and sleep disturbance may contribute to the pathogenesis and progression of Parkinsons Disease. Int. J. Mol. Sci., 2022, 23(21), 12928. doi: 10.3390/ijms232112928 PMID: 36361716
- Dong-Chen, X.; Yong, C.; Yang, X.; Chen-Yu, S.; Li-Hua, P. Signaling pathways in Parkinsons disease: Molecular mechanisms and therapeutic interventions. Signal Transduct. Target. Ther., 2023, 8(1), 73. doi: 10.1038/s41392-023-01353-3 PMID: 36810524
- Forloni, G. Alpha synuclein: Neurodegeneration and inflammation. Int. J. Mol. Sci., 2023, 24(6), 5914. doi: 10.3390/ijms24065914 PMID: 36982988
- Castonguay, A-M.; Gravel, C.; Lévesque, M. Treating Parkinsons Disease with antibodies: Previous studies and future directions. J. Parkinsons Dis., 2021, 11(1), 71-92. doi: 10.3233/JPD-202221
- Knecht, L.; Folke, J.; Dodel, R.; Ross, J.A.; Albus, A. Alpha-synuclein immunization strategies for synucleinopathies in clinical studies: A biological perspective. Neurotherapeutics, 2022, 19(5), 1489-1502. doi: 10.1007/s13311-022-01288-7 PMID: 36083395
- Gupta, V.; Salim, S.; Hmila, I.; Vaikath, N.N.; Sudhakaran, I.P.; Ghanem, S.S.; Majbour, N.K.; Abdulla, S.A.; Emara, M.M.; Abdesselem, H.B.; Lukacsovich, T.; Erskine, D.; El-Agnaf, O.M.A. Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity. Sci. Rep., 2020, 10(1), 8137. doi: 10.1038/s41598-020-65035-8 PMID: 32424162
- Gupta, V.; Sudhakaran, I.P.; Islam, Z.; Vaikath, N.N.; Hmila, I.; Lukacsovich, T.; Kolatkar, P.R.; El-Agnaf, O.M.A. Expression, purification and characterization of α-synuclein fibrillar specific scFv from inclusion bodies. PLoS One, 2020, 15(11), e0241773. doi: 10.1371/journal.pone.0241773 PMID: 33156828
- Fassler, M.; Benaim, C.; George, J. A single chain fragment variant binding misfolded alpha-synuclein exhibits neuroprotective and antigen-specific anti-inflammatory properties. Cells, 2022, 11(23), 3822. doi: 10.3390/cells11233822 PMID: 36497081
- Hmila, I.; Vaikath, N.N.; Majbour, N.K.; Erskine, D.; Sudhakaran, I.P.; Gupta, V.; Ghanem, S.S.; Islam, Z.; Emara, M.M.; Abdesselem, H.B.; Kolatkar, P.R.; Achappa, D.K.; Vinardell, T.; El-Agnaf, O.M.A. Novel engineered nanobodies specific for N-terminal region of alpha-synuclein recognize Lewy‐body pathology and inhibit in-vitro seeded aggregation and toxicity. FEBS J., 2022, 289(15), 4657-4673. doi: 10.1111/febs.16376 PMID: 35090199
- Cookson, M.R. LRRK2 pathways leading to neurodegeneration. Curr. Neurol. Neurosci. Rep., 2015, 15(7), 42. doi: 10.1007/s11910-015-0564-y PMID: 26008812
- Gilligan, P. Inhibitors of leucine-rich repeat kinase 2 (LRRK2): Progress and promise for the treatment of Parkinsons disease. Curr. Top. Med. Chem., 2015, 15(10), 927-938. doi: 10.2174/156802661510150328223655 PMID: 25832719
- Mata, I.; Salles, P.; Cornejo-Olivas, M.; Saffie, P.; Ross, O.A.; Reed, X.; Bandres-Ciga, S. LRRK2: Genetic mechanisms vs genetic subtypes. Handb. Clin. Neurol., 2023, 193, 133-154. doi: 10.1016/B978-0-323-85555-6.00018-7 PMID: 36803807
- Taymans, J.M.; Greggio, E. LRRK2 kinase inhibition as a therapeutic strategy for Parkinsons disease, where do we stand? Curr. Neuropharmacol., 2016, 14(3), 214-225. doi: 10.2174/1570159X13666151030102847 PMID: 26517051
- Singh, R.K.; Soliman, A.; Guaitoli, G.; Störmer, E.; von Zweydorf, F.; Dal Maso, T.; Oun, A.; Van Rillaer, L.; Schmidt, S.H.; Chatterjee, D.; David, J.A.; Pardon, E.; Schwartz, T.U.; Knapp, S.; Kennedy, E.J.; Steyaert, J.; Herberg, F.W.; Kortholt, A.; Gloeckner, C.J.; Versées, W. Nanobodies as allosteric modulators of Parkinsons diseaseassociated LRRK2. Proc. Natl. Acad. Sci., 2022, 119(9), e2112712119. doi: 10.1073/pnas.2112712119 PMID: 35217606
- Rüb, U.; Vonsattel, J.P.G.; Heinsen, H.; Korf, H.W. The neuropathology of Huntingtons disease: Classical findings, recent developments and correlation to functional neuroanatomy. Adv. Anat. Embryol. Cell Biol., 2015, 217, 1-146. doi: 10.1007/978-3-319-19285-7 PMID: 26767207
- Palaiogeorgou, A.; Papakonstantinou, E.; Golfinopoulou, R.; Sigala, M.; Mitsis, T.; Papageorgiou, L.; Diakou, I.; Pierouli, K.; Dragoumani, K.; Spandidos, D.; Bacopoulou, F.; Chrousos, G.; Eliopoulos, E.; Vlachakis, D. Recent approaches on Huntingtons disease (Review). Biomed. Rep., 2022, 18(1), 5. doi: 10.3892/br.2022.1587 PMID: 36544856
- Khoshnan, A.; Ou, S.; Ko, J.; Patterson, P.H. Antibodies and intrabodies against huntingtin: production and screening of monoclonals and single-chain recombinant forms. Methods Mol. Biol., 2013, 1010, 231-251. doi: 10.1007/978-1-62703-411-1_15 PMID: 23754229
- Denis, H.L.; David, L.S.; Cicchetti, F. Antibody-based therapies for Huntingtons disease: Current status and future directions. Neurobiol. Dis., 2019, 132, 104569. doi: 10.1016/j.nbd.2019.104569 PMID: 31398458
- Amaro, I.A.; Henderson, L.A. An intrabody drug (rAAV6-INT41) reduces the binding of N-terminal huntingtin fragment(s) to DNA to basal levels in PC12 cells and delays cognitive loss in the R6/2 animal model. J. Neurodegener. Dis., 2016, 2016, 1-10. doi: 10.1155/2016/7120753 PMID: 27595037
- Perche, F.; Uchida, S.; Akiba, H.; Lin, C.Y.; Ikegami, M.; Dirisala, A.; Nakashima, T.; Itaka, K.; Tsumoto, K.; Kataoka, K. Improved brain expression of anti-amyloid β scFv by complexation of mRNA including a secretion sequence with PEG-based block catiomer. Curr. Alzheimer Res., 2017, 14(3), 295-302. doi: 10.2174/1567205013666161108110031 PMID: 27829339
- Xie, J.; Gonzalez-Carter, D.; Tockary, T.A.; Nakamura, N.; Xue, Y.; Nakakido, M.; Akiba, H.; Dirisala, A.; Liu, X.; Toh, K.; Yang, T.; Wang, Z.; Fukushima, S.; Li, J.; Quader, S.; Tsumoto, K.; Yokota, T.; Anraku, Y.; Kataoka, K. Dual-sensitive nanomicelles enhancing systemic delivery of therapeutically active antibodies specifically into the brain. ACS Nano, 2020, 14(6), 6729-6742. doi: 10.1021/acsnano.9b09991 PMID: 32431145
- Tsitokana, M.E.; Lafon, P.A.; Prézeau, L.; Pin, J.P.; Rondard, P. Targeting the brain with single-domain antibodies: Greater potential than stated so far? Int. J. Mol. Sci., 2023, 24(3), 2632. doi: 10.3390/ijms24032632 PMID: 36768953
- Hultqvist, G.; Syvänen, S.; Fang, X.T.; Lannfelt, L.; Sehlin, D. Bivalent brain shuttle increases antibody uptake by monovalent binding to the transferrin receptor. Theranostics, 2017, 7(2), 308-318. doi: 10.7150/thno.17155 PMID: 28042336
- Meier, S.R.; Syvänen, S.; Hultqvist, G.; Fang, X.T.; Roshanbin, S.; Lannfelt, L.; Neumann, U.; Sehlin, D. Antibody-based in vivo PET imaging detects amyloid-β reduction in alzheimer transgenic mice after BACE-1 inhibition. J. Nucl. Med., 2018, 59(12), 1885-1891. doi: 10.2967/jnumed.118.213140 PMID: 29853653
- Fang, X.T.; Hultqvist, G.; Meier, S.R.; Antoni, G.; Sehlin, D.; Syvänen, S. High detection sensitivity with antibody-based PET radioligand for amyloid beta in brain. Neuroimage, 2019, 184, 881-888. doi: 10.1016/j.neuroimage.2018.10.011 PMID: 30300753
- Stocki, P.; Szary, J.; Rasmussen, C.L.M.; Demydchuk, M.; Northall, L.; Logan, D.B.; Gauhar, A.; Thei, L.; Moos, T.; Walsh, F.S.; Rutkowski, J.L. Blood‐brain barrier transport using a high affinity, brain‐selective VNAR antibody targeting transferrin receptor 1. FASEB J., 2021, 35(2), e21172. doi: 10.1096/fj.202001787R PMID: 33241587
- Syvänen, S.; Fang, X.T.; Hultqvist, G.; Meier, S.R.; Lannfelt, L.; Sehlin, D. A bispecific Tribody PET radioligand for visualization of amyloid-beta protofibrils a new concept for neuroimaging. Neuroimage, 2017, 148, 55-63. doi: 10.1016/j.neuroimage.2017.01.004 PMID: 28069541
- Rofo, F.; Meier, S.R.; Metzendorf, N.G.; Morrison, J.I.; Petrovic, A.; Syvänen, S.; Sehlin, D.; Hultqvist, G. A brain-targeting bispecific-multivalent antibody clears soluble amyloid-beta aggregates in alzheimers disease mice. Neurotherapeutics, 2022, 19(5), 1588-1602. doi: 10.1007/s13311-022-01283-y PMID: 35939261
- Sehlin, D.; Stocki, P.; Gustavsson, T.; Hultqvist, G.; Walsh, F.S.; Rutkowski, J.L.; Syvänen, S. Brain delivery of biologics using a cross-species reactive transferrin receptor 1 VNAR shuttle. FASEB J., 2020, 34(10), 13272-13283. doi: 10.1096/fj.202000610RR PMID: 32779267
- Clarke, E.; Stocki, P.; Sinclair, E.H.; Gauhar, A.; Fletcher, E.J.R.; Krawczun-Rygmaczewska, A.; Duty, S.; Walsh, F.S.; Doherty, P.; Rutkowski, J.L. A single domain shark antibody targeting the transferrin receptor 1 delivers a TrkB agonist antibody to the brain and provides full neuroprotection in a mouse model of Parkinsons Disease. Pharmaceutics, 2022, 14(7), 1335. doi: 10.3390/pharmaceutics14071335 PMID: 35890231
- Wouters, Y.; Jaspers, T.; Rué, L.; Serneels, L.; De Strooper, B.; Dewilde, M. VHHs as tools for therapeutic protein delivery to the central nervous system. Fluids Barriers CNS, 2022, 19(1), 79. doi: 10.1186/s12987-022-00374-4 PMID: 36192747
- Alata, W.; Yogi, A.; Brunette, E.; Delaney, C.E.; Faassen, H.; Hussack, G.; Iqbal, U.; Kemmerich, K.; Haqqani, A.S.; Moreno, M.J.; Stanimirovic, D.B. Targeting insulin‐like growth factor‐1 receptor (IGF1R) for brain delivery of biologics. FASEB J., 2022, 36(3), e22208. doi: 10.1096/fj.202101644R PMID: 35192204
- Yogi, A.; Hussack, G.; van Faassen, H.; Haqqani, A.S.; Delaney, C.E.; Brunette, E.; Sandhu, J.K.; Hewitt, M.; Sulea, T.; Kemmerich, K.; Stanimirovic, D.B. Brain delivery of IGF1R5, a single-domain antibody targeting insulin-like growth factor-1 receptor. Pharmaceutics, 2022, 14(7), 1452. doi: 10.3390/pharmaceutics14071452 PMID: 35890347
- Aguiar, S.I.; Días, J.N.R.; André, A.S.; Silva, M.L.; Martins, D.; Carrapiço, B.; Castanho, M.; Carriço, J.; Cavaco, M.; Gaspar, M.M.; Nobre, R.J.; Pereira de Almeida, L.; Oliveira, S.; Gano, L.; Correia, J.D.G.; Barbas, C., III; Gonçalves, J.; Neves, V.; Aires-da-Silva, F. Highly specific blood-brain barrier transmigrating single-domain antibodies selected by an in vivo phage display screening. Pharmaceutics, 2021, 13(10), 1598. doi: 10.3390/pharmaceutics13101598 PMID: 34683891
- Vangijzegem, T.; Lecomte, V.; Ternad, I.; Van Leuven, L.; Muller, R.N.; Stanicki, D.; Laurent, S. Superparamagnetic iron oxide nanoparticles (SPION): From fundamentals to state-of-the-art innovative applications for cancer therapy. Pharmaceutics, 2023, 15(1), 236. doi: 10.3390/pharmaceutics15010236 PMID: 36678868
- Liu, X.; Lu, S.; Liu, D.; Zhang, L.; Zhang, L.; Yu, X.; Liu, R. ScFv-conjugated superparamagnetic iron oxide nanoparticles for MRI-based diagnosis in transgenic mouse models of Parkinsons and Huntingtons diseases. Brain Res., 2019, 1707, 141-153. doi: 10.1016/j.brainres.2018.11.034 PMID: 30481502
- Liu, X.G.; Zhang, L.; Lu, S.; Liu, D.Q.; Zhang, L.X.; Yu, X.L.; Liu, R.T. Multifunctional superparamagnetic iron oxide nanoparticles conjugated with Aβ oligomer-specific scFv antibody and class a scavenger receptor activator show early diagnostic potentials for Alzheimers Disease. Int. J. Nanomedicine, 2020, 15, 4919-4932. doi: 10.2147/IJN.S240953 PMID: 32764925
- Liu, X.; Zhang, L.; Lu, S.; Liu, D.; Huang, Y.; Zhu, J.; Zhou, W.; Yu, X.; Liu, R. Superparamagnetic iron oxide nanoparticles conjugated with Aβ oligomer-specific scFv antibody and class A scavenger receptor activator show therapeutic potentials for Alzheimers disease. J. Nanobiotechnology, 2020, 18(1), 160. doi: 10.1186/s12951-020-00723-1 PMID: 33160377
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