Publications

The technologies and innovative tools and discovery platforms employed by ND-BioSciences are based on more than 15 years of innovation and pioneering work that was carried out in the laboratory of its founder, Dr. Hilal A. Lashuel and are well-documented in several high impact peer-reviewed publications. 
Key publications related to ND-BioSciences technologies and research discovery and development platforms.
Alzheimer’s Disease: Amyloid-beta/Tau
Parkinson’s Disease: Alpha-Synuclein
Huntington’s Disease: Huntingtin
Biomarkers discovery
Aggregation inhibitors and Modulators
Cellular and Neuronal Models of Toxicity
Protein Synthesis



Alzheimer’s Disease: Amyloid-beta

Eleuteri S, Di Giovanni S, Rockenstein E, Mante M, Adame A, Trejo M, Wrasidlo W, Wu F, Fraering PC, Masliah E, Lashuel HA*. Novel therapeutic strategy for neurodegeneration by blocking Aβ seeding mediated aggregation in models of Alzheimer’s disease. Neurobiology of Disease. 2015, 74:144-57.

Droste P, Frenzel A, Steinwand M, Pelat T, Thullier P, Hust M, Lashuel HA*, Dübel S*. Structural differences of Amyloid-b fibrils revealed by antibodies from phage display. BMC Biotechnology. 2015;15(1):57. doi: 10.1186/s12896-015-0146-8.

Jeong JS, Ansaloni A, Mezzenga R, Lashuel HA*, and Dietler G*. Novel mechanistic insight into the molecular basis of amyloid polymorphism and secondary nucleation during amyloid formation. Journal of Molecular Biology. 2013, 425(10):1765-81.

Jan A and Lashuel HA*. Biophysical Approaches for Establishing the Links between Aβ aggregation and toxicity. Methods in Molecular Biology. 2012, 849, 227-43

Jan A, Adolfsson O, Allaman I, Buccarello AL, Magistretti PJ, Pfeifer A, Muhs A, Lashuel HA*. Aβ42 neurotoxicity is mediated by ongoing nucleated polymerization process rather than by discrete Aβ42 species. Journal of Biological Chemistry. 2011, 286(10):8585-96.

Di Giovanni S, Eleuteri SC, Paeologou KE, Zweckstetter M, Carrupt PA, Lashuel HA*. Entacapone and Tolcapone, two catechol‑O‑methyltransferase inhibitors, block fibril formation of a-syn and Aβ and protect against amyloid induced toxicity. Journal of Biological Chemistry. 2010, 285(20):14941-54.

Jan A, Hartley DM and Lashuel HA*. Preparation and characterization of toxic Aβ intermediates for structural and functional studies in Alzheimer’s disease research. Nature Protocols. 2010;5(6):1186-209.  

Jan A, Goekce Ol, Luthi-Carter R, and Lashuel HA*. The ratio of monomeric/ aggregatedforms of Ab (40&42) is an important determinant of Ab aggregation and fibrillogenesis in Alzheimer’s diseases. Journal of Biological Chemistry. 2008, 283(42):28176-89.

Arimon M., Grimminger V., Sanz F, Lashuel HA*. Hsp104 targets multiple intermediates on the amyloid pathway and suppresses the seeding capacity of fibrils and protofibrils of Aβ. Journal [MA2] of Molecular Biology. 2008, 384(5):1157-1173.

Lansbury PT* and Lashuel HA*. A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature. 2006, 443, 774-779.

Lashuel HA*, Hartley D, Petre B, Wall, Simon M, Walz T, Lansbury PT. Mixtures of wild-type and a pathogenic (E22G) form of A40 in vitro accumulate protofibrils, including amyloid pores. Journal of Molecular Biology. 2003, 332, 795-808.

Tau

Haj-Yahya M and Lashuel HA*. Protein semisynthesis provides access to Tau disease-associated post-translational modifications (PTMs) and paves the way to deciphering the Tau PTM code in health and disease states. Journal of the American Chemical Society (JACS). 2018, I Apr 23. doi: 10.1021/jacs.8b02668.

Ait-Bouziad N, Lv G, Mahul-Mellier AL, Xiao S, Zorludemir G, Eliezer D, Walz Tand Lashuel HA*. Discovery and Characterization of Novel Stable Tau Oligomeric Complexes: Implications for the Role of Tau/Phospholipid Interactions in Regulating its Functions in Health and Disease. Nature Communications. 2017, 8, 1, 1678, 2017.

Adamcik J, Sánchez-Ferrer A, Ait-Bouziad N, Reynolds NP, Lashuel HA*, Mezzenga R*. Microtubule-Binding R3 Fragment from Tau Self-Assembles into Giant Multistranded Amyloid Ribbons. Angewandte Chem. Int. Ed. 2016, 11;55(2):618-22.



Parkinson’s Disease: Alpha-Synuclein

Anne-Laure Mahul-Mellier, Firat Altay, Johannes Burtscher et al. The making of a Lewy body: the role of alpha-synuclein post-fibrillization modifications in regulating the formation and maturation of pathological inclusions. BioRxiv, 2018, doi: https://doi.org/10.1101/500058

Burtscher J, Copin JC., Rodriguez J., Kumar ST, Chiki A, Guillot de Suduiraut MI, Sandi C., and Lashuel HA*. Chronic corticosterone enhancement aggravates alpha-synuclein brain spreading pathology and substantia nigra neurodegeneration in mice”. BioRxiv, 2019. doi:https://doi.org/10.1101/469999

El Turk F, De Genst E, Guilliams T, Fauvet B, Hejjaoui M, Vendruscolo M*, Lashuel HA*, Dobson CM*. “Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding”. Protein Science. 2018, (7):1262-1274.

Dikiy I, Fauvet B, Jovičić A, Mahul-Mellier A, Desorby C, El-Turk F, Gitler AD, Lashuel HA*, Eliezer D*. Semisynthetic and in vitro phosphorylation of alpha-synuclein at Y39 promotes functional partly-helical membrane-bound states resembling those induced by PD mutations. ACS Chem Biol. 2016, 11(9):2428-37.

Fares MB, Maco B, Oueslati A, Rockenstein  E, Ninkina N, Buchman V, Masliah E, Lashuel HA*. Induction of de novo α-Synuclein fibrillization in a novel neuronal model for Parkinson’s disease. Proceedings of the National Academy of Sciences. 2016, 16;113(7): E912-21.

Mahul-Mellier A, Vercruysse F, Maco B, Ait-Bouziad N, De Roo M, Muller D and Lashuel HA*. Fibril growth and seeding capacity play key roles in α-synuclein-mediated apoptotic cell death. Cell Death and Differentiation. 2015, (12):2107-22.

Mbefo MK, Fares MB, Paleologou K, Oueslati A, Yin G, Tenreiro S, Pinto M, Outeiro T, Zweckstetter M, Masliah E, Lashuel HA*. Parkinson Disease Mutant E46K Enhances α-Synuclein Phosphorylation in Mammalian Cell Lines, in Yeast, and in Vivo. Journal of Biological Chemistry. 2015 Apr 10;290(15):9412-27.

Fares MB, Ait-Bouziad N, Dikiy I, Mbefo MK, Jovičić A, Kiely A, Holton JL, Lee SJ, Gitler AD, Eliezer D, Lashuel HA*. The novel Parkinson’s disease linked mutation G51D attenuates in vitro aggregation and membrane binding of α-synuclein, and enhances its secretion and nuclear localization in cells. Human Molecular Genetics. 2014, 23(17):4491-509.

Mahul-Mellier AL, Fauvet B, Gysbers A, Dikiy I, Oueslati A, Georgeon S, Lamontanara AJ, Bisquertt A, Eliezer D, Masliah E, Halliday G, Hantschel O, Lashuel HA*. c-Abl phosphorylates a-synuclein and regulates its degradation: implications for a-syn clearance and contribution to the pathogenesis of Parkinson’s disease. Human Molecular Genetics. 2014, 23(11): 2858-79.

Oueslati A, Schneider BL, Aebischer P, and Lashuel HA*. PLK2 regulates selective autophagic clearance of a-synuclein and suppresses its toxicity. Proceedings of the National Academy of Sciences. 2013, 110(41):E3945-54.

Haj-Yahia M, Fauvet B, Herman-Badhinsky Y, Hejjaoui M, Bavikar SN, Vedhanarayanan K, Ciechanover A*, Lashuel HA* and Brik A*. Synthetic polyubiquitin alpha-synuclein reveals important insights into the roles of the ubiquitin chain in regulating its pathophysiology., Proceedings of the National Academy of Sciences. 2013, 110(44):17726-31

Fauvet B, Butterfield SM, Fuks J, Brik A, and Lashuel HA*. One-pot total chemical synthesis of alpha-synulein. Chem Commu. 2013, 49 (81), 9254 – 9256.

Schmid A, Fauvet B, Moniatte M, and Lashuel HA*. Alpha-synuclein post-translational modifications as potential biomarkers for Parkinson’s disease and other synucleinopathies., Molecular and Cellular Proteomics. 2013, 12(12):3543-58.

Lashuel HA, Overk C, Ouelati A, and Masliah E. α-synuclein oliogmerizatoin in health and disease. Nature Review Neuroscience. 2013 Jan;14(1):38-48.

Shabek N, Herman-Bachinsky Y, Buchsbaum S, Lewinson O, Haj-Yahya M, Hejjaoui M, Lashuel HA, Sommer T, Brik A, Ceichanover A. The size of the proteasomal substrate determines whether its degradation will be mediated by Mono- or Polyubiquitination. Mol. Cell. 2012, 12;48(1):87-97

Hejjaoui M, Butterfield S, Fauvet B, Vercryusse F, Cun J, Dikiy I, Prudent M, Olschewski D, Zhang Y, Eliezer D, Lashuel HA*.  Chemical Biology of α-synuclein: Elucidating the role of C-terminal post-translational modifications using protein semisynthetic strategies: Phosphorylation at Tyrosine 125. Journal of the American Chemical Society. 2012. 21;134(11):5196-210.

Oueslati A, Paleologou KE, Schneider BL, Aebischer P, Lashuel HA*. Mimicking phosphorylation at Serin87 inhibits the aggregation of human alpha-synuclein and protects against its toxicity in a rat model of Parkinson’s disease. Journal of Neuroscience. 2012, 1;32(5):1536-44.

Fauvet B., Mebfo MK, Fares BM, Desobry C, Michael S, Ardah MT, Tsika E, Coune P, Eliezer D, Moore DJ, Schneider B, Aebischer P., El-agnaf OM, Masliah E, and Lashuel HA*. Alpha-synuclein in the central nervous system, in mammalian cells, and produced by E. coli exists predominantly as a disorderd monomer. Journal of Biological Chemistry. 2012, 287, 15345-15364

Fauvet B, Fares BM, Samuel F, Kikiy I, Tandon A, Eliezer D, Lashuel HA*. Characterization of semisynthetic and natural N-terminal acetylated α-synuclein in vitro and in intact cells: Iimplications for a-synuclein aggregation and cellular properties. Journal of Biological Chemistry. 2012, 17;287(34):28243-62.

Hejjaoui H, Haj-Yahya M, Kumar KS, Brik A*, Lashuel HA*. Towards elucidating the role of ubiquitination in the pathogenesis of Parkinson’s disease using semisynthetic ubquitinated α-synuclein. Angewandte Chem Int Ed. 2011, 10;50(2):405-9.

Paleologou KE, Oueslati A, Kim HY, Lamberto GR, Rospigliosi CC, Schmid A, Chiappe D, Moniatte M, Eliezer D, Zweckstetter M, Masliah E, Lashuel HA*. Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions. Journal of Neuroscience. 2010, 3;30(9):3184-98.

Mbefo MK, Paleologou KE, Boucharaba A, Oueslati A, Olschewski D, Schell H, Fournier M, Zweckstetter M., Kahle PJ, Masliah E Hirling H, Lashuel HA*. Phosphorylation of synucleins (α, β and g) by members of the Polo Like family of Kinases, PLKs 1-4. Journal of Biological Chemistry. 2010, 285(4):2807-22.

Oueslati A, Fournier M, and Lashuel HA*. Role of post-translational modifications in modulating α-synuclein structure, aggregation and toxicity: implications for Parkinson’s disease pathogenesis and therapies. Progress in Brain Research. 2010;183C:115-145.

Lashuel HA*, Petre B, Wall, Simon M, Nowak RJ, Walz T, Lansbury PT. -Synuclein, Especially the Parkinson’s Disease-Associated Mutants, Form Pore-like Annular and Tubular Protofibrils.  J. Mol. Biol. 2002. 322, 5, 1089-1102.


Huntington’s Disease: Huntingtin

DeGuire SM, Ruggeri SM,Fares MF,Cendrowska U,Dietler G,and Lashuel HA*. Phosphorylation at S13 and/or S16 strongly inhibits the aggregation of mutant Httex1, regulates its helical conformation and prompts the internalization and nuclear targeting of preformed Httex1aggregates. Journal of Biological Chemistry. 2018, 293(48):18540-18558.

Reif A, Chiki A, Ricci J, and Lashuel HA*. Generation of native, untagged Huntingtin Exon1 monomers and fibrils using a SUMO fusion strategy. Journal of Visualized Experiments. 2018, 136, doi: 10.3791/5706.

Cariulo C, Azzollini L, Verani M, Martufi P, Chiki A, Deguire SM, Cherubini M, Gines S, Marsh LJ, Lavery D, Doherty E, Conforti P, Cattaneo E, Santimone J, Squitieri F, Lashuel HA*, Petricca L*, and Caricasole A*. Phosphorylation of huntingtin at residue T3 is decreased in Huntington’s disease and modulates mutant huntingtin protein conformation, Proceedings of the National Academy of Sciences. 2017, 114(50): E10809-E10818.

Warner J, Ruff K, Tan P, Lemke E, Pappu R* and Lashuel HA*. Monomeric huntingtin exon 1 has similar overall structural features for wild type and pathological polyglutamine lengths. Journal of the American Chemical Society, 2017, 139(41):14456-14469.

Chiki A.,DeGuire SM., Ruggeri SF.,Cendrowska U.,Ansaloni A.,Wang Z.,  Sanfelice D.,Burai R.,Vieweg S.,Pastore A.,Dietler G., and Lashuel HA*. Mutant Exon1 huntingtin aggregation is regulated by T3 phosphorylation-induced structural changes and cross-talk between T3 phosphorylation and acetylation at K6. Angewandte Chem. Int. Ed. 2017, 56(19): 5202-5207.

Ansaloni A, Wang ZM, Jeong JS, Ruggeri FS, Dietler G, Lashuel HA*. One-pot semisynthesis of Exon1 of the Huntingtin protein: new tools for elucidating the role of post-translational modifications in the pathogenesis of Huntington’s disease. Angewandte Chem Int. Ed. Engl. 2014, 10;53(7):1928-33.

Wang Z and Lashuel HA*. Discovery of a novel aggregation domain in the Huntingtin Protein: Implications for the mechanisms of Htt aggregation and toxicity. 2013, Angewandte Chem. Int. Ed. 2013 Jan 7;52(2):562-7.


Biomarkers discovery

lenhauer B, Bowman F, Daniel D,  DziadeK S, Blennow K, Corradini K ; El-Agnaf O, Shaw L, Masucci J, Taylor P, Umek RM, Stoops E, Vanderstichele H, Schmid AW, Moniatte M, Zhang J, Kruse N, Lashuel HA, Dave DK, Hutten SJ, Zetterberg H. Immunochemical methods for the measurement of a-synuclein concentration in human cerebrospinal fluid – method comparisons and round robin studies. J. Neurochemistry. 2019, 149(1):126-138. 

Mollenhauer B, Batrla B, El-Agnaf O, Galasko DR, Lashuel HA, Merchant KM, Shaw LM, Selkoe DJ, Umek R, Vanderstichele H, Zetterberg H, Zhang J, Caspell-Garcia C, Coffey C, Hutten SJ, Frasier M, Taylor P for the Investigating Synuclein Consortium of the Michael J. Fox Foundation for Parkinson’s Research. A user’s guide for α-synuclein biomarker studies in biological fluids: Peri-analytical considerations. Journal of Movement Disorder. 2017, 32(8):1117-1130.

Schmid A, Fauvet B, Moniatte M, and Lashuel HA*. Alpha-synuclein post-translational modifications as potential biomarkers for Parkinson’s disease and other synucleinopathies., Molecular and Cellular Proteomics. 2013, 12(12):3543-58.


 Aggregation inhibitors and Modulators

Levine PM, Galesic A, Balana AT, Mahul AL, Navarro MX, Lashuel HA, Pratt MR. O-GlcNAc modification of α-synuclein alters protein aggregation and neuronal toxicity, revealing glycosylation of specific residues as key potential inhibitors of the progression of Parkinson’s disease. Proceedings of the National Academy of Sciences. 2019, 116(5):1511-1519.

Oueslati A, Schneider BL, Aebischer P, and Lashuel HA*. PLK2 regulates selective autophagic clearance of a-synuclein and suppresses its toxicity. Proceedings of the National Academy of Sciences. 2013, 110(41):E3945-54.

Eleuteri S, Di Giovanni S, Rockenstein E, Mante M, Adame A, Trejo M, Wrasidlo W, Wu F, Fraering PC, Masliah E, Lashuel HA*. Novel therapeutic strategy for neurodegeneration by blocking Aβ seeding mediated aggregation in models of Alzheimer’s disease. Neurobiology of Disease. 2015, 74:144-57.

Di Giovanni S, Eleuteri SC, Paeologou KE, Zweckstetter M, Carrupt PA, Lashuel HA*. Entacapone and Tolcapone, two catechol‑O‑methyltransferase inhibitors, block fibril formation of a-syn and Aβ and protect against amyloid induced toxicity. Journal of Biological Chemistry. 2010, 285(20):14941-54.

Arimon M., Grimminger V., Sanz F, Lashuel HA*. Hsp104 targets multiple intermediates on the amyloid pathway and suppresses the seeding capacity of fibrils and protofibrils of Aβ. Journal [MA1] of Molecular Biology. 2008, 384(5):1157-1173.



Cellular and Neuronal Models of Toxicity

Anne-Laure Mahul-Mellier, Firat Altay, Johannes Burtscher et al. The making of a Lewy body: the role of alpha-synuclein post-fibrillization modifications in regulating the formation and maturation of pathological inclusions. BioRxiv, 2018, doi: https://doi.org/10.1101/500058

Levine PM, Galesic A, Balana AT, Mahul AL, Navarro MX, Lashuel HA, Pratt MR. O-GlcNAc modification of α-synuclein alters protein aggregation and neuronal toxicity, revealing glycosylation of specific residues as key potential inhibitors of the progression of Parkinson’s disease. Proceedings of the National Academy of Sciences. 2019, 116(5):1511-1519.

Ait-Bouziad N, Lv G, Mahul-Mellier AL, Xiao S, Zorludemir G, Eliezer D, Walz Tand Lashuel HA*. Discovery and Characterization of Novel Stable Tau Oligomeric Complexes: Implications for the Role of Tau/Phospholipid Interactions in Regulating its Functions in Health and Disease. Nature Communications. 2017, 8, 1, 1678, 2017.

Fares MB, Maco B, Oueslati A, Rockenstein  E, Ninkina N, Buchman V, Masliah E, Lashuel HA*. Induction of de novo α-Synuclein fibrillization in a novel neuronal model for Parkinson’s disease. Proceedings of the National Academy of Sciences. 2016, 16;113(7): E912-21.

Mahul-Mellier A, Vercruysse F, Maco B, Ait-Bouziad N, De Roo M, Muller D and Lashuel HA*. Fibril growth and seeding capacity play key roles in α-synuclein-mediated apoptotic cell death. Cell Death and Differentiation. 2015, (12):2107-22.


Protein Synthesis

DeGuire SM, Ruggeri SM,Fares MF,Cendrowska U,Dietler G,and Lashuel HA*. Phosphorylation at S13 and/or S16 strongly inhibits the aggregation of mutant Httex1, regulates its helical conformation and prompts the internalization and nuclear targeting of preformed Httex1aggregates. Journal of Biological Chemistry. 2018, 293(48):18540-18558.

Haj-Yahya M and Lashuel HA*. Protein semisynthesis provides access to Tau disease-associated post-translational modifications (PTMs) and paves the way to deciphering the Tau PTM code in health and disease states. Journal of the American Chemical Society (JACS). 2018, I Apr 23. doi: 10.1021/jacs.8b02668.

Warner J, Ruff K, Tan P, Lemke E, Pappu R* and Lashuel HA*. Monomeric huntingtin exon 1 has similar overall structural features for wild type and pathological polyglutamine lengths. Journal of the American Chemical Society, 2017, 139(41):14456-14469.

Chiki A.,DeGuire SM., Ruggeri SF.,Cendrowska U.,Ansaloni A.,Wang Z.,  Sanfelice D.,Burai R.,Vieweg S.,Pastore A.,Dietler G., and Lashuel HA*. Mutant Exon1 huntingtin aggregation is regulated by T3 phosphorylation-induced structural changes and cross-talk between T3 phosphorylation and acetylation at K6. Angewandte Chem. Int. Ed. 2017, 56(19): 5202-5207.

Fauvet B and Lashuel HA*. Semisynthesis and enzymatic preparation of post-translationally modified α-Synuclein. Methods in Molecular Biology. 2016, 1345:3-20.

Dikiy I, Fauvet B, Jovičić A, Mahul-Mellier A, Desorby C, El-Turk F, Gitler AD, Lashuel HA*, Eliezer D*. Semisynthetic and in vitro phosphorylation of alpha-synuclein at Y39 promotes functional partly-helical membrane-bound states resembling those induced by PD mutations. ACS Chem Biol. 2016, 11(9):2428-37.

Haj-Yahia M, Fauvet B, Herman-Badhinsky Y, Hejjaoui M, Bavikar SN, Vedhanarayanan K, Ciechanover A*, Lashuel HA* and Brik A*. Synthetic polyubiquitin alpha-synuclein reveals important insights into the roles of the ubiquitin chain in regulating its pathophysiology., Proceedings of the National Academy of Sciences. 2013, 110(44):17726-31

Shabek N, Herman-Bachinsky Y, Buchsbaum S, Lewinson O, Haj-Yahya M, Hejjaoui M, Lashuel HA, Sommer T, Brik A, Ceichanover A. The size of the proteasomal substrate determines whether its degradation will be mediated by Mono- or Polyubiquitination. Mol. Cell. 2012, 12;48(1):87-97

Hejjaoui M, Butterfield S, Fauvet B, Vercryusse F, Cun J, Dikiy I, Prudent M, Olschewski D, Zhang Y, Eliezer D, Lashuel HA*.  Chemical Biology of α-synuclein: Elucidating the role of C-terminal post-translational modifications using protein semisynthetic strategies: Phosphorylation at Tyrosine 125. Journal of the American Chemical Society. 2012. 21;134(11):5196-210.

Fauvet B, Fares BM, Samuel F, Kikiy I, Tandon A, Eliezer D, Lashuel HA*. Characterization of semisynthetic and natural N-terminal acetylated α-synuclein in vitro and in intact cells: Iimplications for a-synuclein aggregation and cellular properties. Journal of Biological Chemistry. 2012, 17;287(34):28243-62.

Hejjaoui H, Haj-Yahya M, Kumar KS, Brik A*, Lashuel HA*. Towards elucidating the role of ubiquitination in the pathogenesis of Parkinson’s disease using semisynthetic ubquitinated α-synuclein. Angewandte Chem Int Ed. 2011, 10;50(2):405-9.

Ansaloni A, Wang ZM, Jeong JS, Ruggeri FS, Dietler G, Lashuel HA*. One-pot semisynthesis of Exon1 of the Huntingtin protein: new tools for elucidating the role of post-translational modifications in the pathogenesis of Huntington’s disease. Angewandte Chem Int. Ed. Engl. 2014, 10;53(7):1928-33.