2023
α-Synuclein Aggregation is Triggered by Amyloid-β Oligomers via Heterogeneous Primary Nucleation
Devkee M. Vadukul, Marcell Papp, Rebecca J. Thrush, Jielei Wang, Yiyun Jin, Paolo Arosio, Francesco A. Aprile
BioRxiv. https://doi.org/10.1101/2022.06.20.496547 Preprint
2022
An antibody scanning method for the detection of α-synuclein oligomers in the serum of Parkinson's disease patients.
Klara Kulenkampff, Derya Emin, Roxine Staats, Yu P. Zhang , Laila Sakhnini, Antonina Kouli, Oded Rimon, Evgeniia Lobanova, Caroline H. Williams-Gray, Francesco A. Aprile, Pietro Sormanni, David Klenerman, Michele Vendruscolo.
Chem. Sci. (2022). 13, 13815-13828. 10.1039/D2SC00066K
A Facile Method to Produce N-Terminally Truncated α-Synuclein.
Rebecca J. Thrush, Devkee M. Vadukul, Francesco A. Aprile.
Front. Neurosci. 16:881480 (2022). 10.3389/fnins.2022.881480
A Chemical Mutagenesis Approach to Insert Post-Translational Modifications in Aggregation-Prone Proteins.
Ying Ge, Athina Masoura, Jingzhou Yang, Francesco A. Aprile.
ACS Chem. Neurosci. 13, 12, 1714-1718 (2022). 10.1021/acschemneuro.2c00077
2021
Man does not live by intrinsically unstructured proteins alone: The role of structured regions in aggregation.
Aprile FA, Temussi PA, Pastore A.
BioEssays. 2100178 (2021). 10.1002/bies.202100178
The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation.
Pras A, Houben B, Aprile FA, Seinstra R, Gallardo R, Janssen L, Hogewerf W, Gallrein C, De Vleeschouwer M, Mata-Cabana A, Koopman M, Stroo E, De Vries M, Edwards S, Kirstein J, Vendruscolo M, Falsone SF, Rousseau F, Schymkowitz J, Nollen EAA.
EMBO J. e107568 (2021). doi.org/10.15252/embj.2020107568
The binding of the small heat-shock protein αB-crystallin to fibrils of α-synuclein is driven by entropic forces.
Scheidt T, Carozza JA, Kolbe CC, Aprile FA, Tkachenko O, Bellaiche MMJ, Meisl G, Peter Q, Herling TW, Ness S, Cruz MC, Benesch JLP, Vendruscolo M, Dobson CM, Arosio P, Knowles TPJ.
Proc. Natl. Acad. Sci. U.S.A. 118, e2108790118 (2021). 10.1073/pnas.2108790118
Modulation of Amyloid-β Aggregation by Metal Complexes with a Dual Binding Mode and Their Delivery across the Blood-Brain Barrier Using Focused Ultrasound
Chan TG, Ruehl CL, Morse SV, Simon M, Rakers V, Watts H, Aprile FA, Choi JJ, Vilar R.
Chem. Sci. 12, 9485-9493 (2021).10.1039/d1sc02273c
The Diagnostic Potential of Amyloidogenic Proteins
Jin Y, Vadukul DM, Gialama D, Ge Y, Thrush R, White JT, Aprile FA
Int. J. Mol. Sci. 22, 4128 (2021). doi:10.3390/ijms22084128
Comparative Studies in the A30P and A53T α-Synuclein C. elegans Strains to Investigate the Molecular Origins of Parkinson's Disease
Perni M, Van Der Goot A, Limbocker R, Van Ham T, Aprile FA, Xu C, Flamgeier P, Thijssen K, Sormanni P, Fusco G, Chen SW, Calla PK, Kirkegaard JB, Laine R, Ma KY, Muller MBD, Sinnige T, Kumita JK, Cohen SIA, Seinstra R, Kaminski Schierle GS, Kaminski CF, Barbut D, De Simone A, Knowles TPJ, Zasloff MA, Nollen E, Vendruscolo M, Dobson CM. Front. Cell Dev. Biol. 9:552549 (2021). 10.3389/fcell.2021.552549
Rationally Designed Bicyclic Peptides Prevent the Conversion of Aβ42 Assemblies into Fibrillar Structures
Ikenoue T, Aprile FA, Sormanni P, Vendruscolo MFront. Neurosci. 15, 623097 (2021). 10.3389/fnins.2021.623097
Systematic Activity Maturation of a Single-Domain Antibody with Non-canonical Amino Acids through Chemical Mutagenesis
Lindstedt PR, Aprile FA, Sormanni P, Rakoto R, Dobson CM, Bernardes GJL, Vendruscolo MCell Chem. Biol. 28, 70-77 (2021). doi:10.1016/j.chembiol.2020.11.002
2020
Small Molecule Sequestration of Amyloid-β as a Drug Discovery Strategy for Alzheimer’s Disease.
Heller GT, Aprile FA, Michaels TCT, Limbocker R, Perni M, Ruggeri FS, Mannini B, Löhr T, Bonomi M, De Simone A, Felli IC, Pierattelli R, Knowles TPJ, Dobson CM, and Vendruscolo M.
Sci. Adv. 6, eabb5924 (2020). 10.1126/sciadv.abb5924
A rationally designed bicyclic peptide remodels Aβ42 aggregation in vitro and reduces its toxicity in a worm model of Alzheimer's disease
Ikenoue T, Aprile FA, Sormanni P, Ruggeri FS, Perni M, Heller GT, Haas CP, Middel C, Limbocker R, Mannini B, Michaels TCT, Knowles TPJ, Dobson CM, Vendruscolo M
Sci. Rep. 10,15280 (2020) doi:10.1038/s41598-020-69626-3
Rationally Designed Antibodies as Research Tools to Study the Structure–Toxicity Relationship of Amyloid-β Oligomers
Limbocker R*, Mannini B, Cataldi R, Chhangur S, Wright AK, Kreiser RP, Albright JA, Chia S, Habchi J, Sormanni P, Kumita JR, Ruggeri FS, Dobson CM, Chiti F, Aprile FA*, Vendruscolo M*
Int. J. Mol. Sci. 21(12), 4542 (2020) doi:10.3390/ijms21124542
Rational design of a conformation-specific antibody for the quantification of Aβ oligomers
Aprile FA*, Sormanni P, Podpolny M, Chhangur S, Needham L-M, Ruggeri FS, Perni M, Limbocker R, Heller GT, Sneideris T, Scheidt T, Mannini B, Habchi J, Lee SF, Salinas PC, Knowles TPJ, Dobson CM, Vendruscolo M*
Proc Natl Acad Sci U S A 117 (24), 13509-13518 (2020); DOI: 10.1073/pnas.1919464117
2019
C. elegans expressing D76N β2-microglobulin: a model for in vivo screening of drug candidates targeting amyloidosis.
Faravelli G, Raimondi S, Marchese L, Partridge FA, Soria C, Mangione P, Canetti D, Perni M, Aprile FA, Zorzoli I, Di Schiavi E, Lomas DA, Bellotti V, Sattelle DB, and Giorgietti S.
Sci. Rep. 9, 19960 (2019) doi: 10.1038/s41598-019-56498-5
Soluble aggregates present in a cerebrospinal fluid change in size and mechanism of toxicity during Alzheimer's disease progression
De S, Whiten DR, Ruggeri FS, Hughes C, Rodrigues M, Sideris DI, Taylor CG, Aprile FA, Muyldermans S, Knowles TPJ, Vendruscolo M, Bryant CE, Blennow K, Skoog I, Kern S, Zetterberg H, and Klenerman D.
Acta Neuropathol. Commun. 7, 120 (2019) doi: 10.1186/s40478-019-0777-4
Enhancement of the Anti-Aggregation Activity of a Molecular Chaperone Using a Rationally Designed Post-Translational Modification
Philip LR, Aprile FA, Matos MJ, Perni M; Bertoldo JB, Bernardim B, Quentin P, Jiménez-Osés G, Gonzalo Knowles TPJ; Dobson CM; Corzana F; Vendruscolo M, and Bernardes G.
ACS Cent. Sci. 5, 1417-1424 (2019) doi: 10.1021/acscentsci.9b00467
Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms
De S*, Wirthensohn DC*, Flagmeier P*, Hughes C*, Aprile FA*, Ruggeri FS*, Whiten DR, Emin D, Xia Z, Varela JA, Sormanni P, Kundel F, Knowles TPJ, Dobson CM, Bryant C, Vendruscolo M, and Klenerman D.
Nat. Commun. 10, 1541 (2019) doi: 10.1038/s41467-019-09477-3
2018
Third generation antibody discovery methods: in silico rational design
Sormanni P, Aprile FA, and Vendruscolo M.
Chem. Soc. Rev. 47, 9137-9157 (2018) doi: 10.1039/c8cs00523k
Automated behavioural analysis of large C. elegans populations using a wide field of view tracking platform
Perni M, Casford S, Aprile FA, Nollen EAA, Knowles TPJ, Vendruscolo M, and Dobson CM.
J. Vis. Exp. 141, e58643 (2018) doi: 10.3791/58643
Targeting amyloid aggregation: an overview of strategies and mechanisms
Giorgetti S, Greco C, Tortora P, and Aprile FA.
Int. J. Mol. Sci. 19, 2677 (2018) doi: 10.3390/ijms19092677
Multistep inhibition of α-synuclein aggregation and toxicity in vitro and in vivo by trodusquemine
Perni M, Flagmeier P, Limbocker R, Cascella R, Aprile FA, Galvagnion C, Heller GT, Meisl G, Chen SW, Kumita JR, Challa PK, Kirkegaard JB, Cohen SIA, Mannini B, Barbut D, Nollen EAA, Cecchi C, Cremades N, Knowles TPJ, Chiti F, Zasloff M, VendruscoloM, and Dobson CM.
ACS Chem. Biol. 13, 2308-2319 (2018) doi: 10.1021/acschembio.8b00466.
Cooperative assembly of Hsp70 subdomain clusters
Wright M, Aprile FA, Bellaiche MMJ, Michaels TCT, Muller T, Arosio P, Vendruscolo M, Dobson CM, and Knowles TPJ.
Biochemistry 57, 3641-3649 (2018) doi: 10.1021/acs.biochem.8b00151
A rationally designed Hsp70 variant rescues the aggregation-associated toxicity of human IAPP in cultured pancreatic islet β-cells
Bongiovanni MN, Aprile FA, Sormanni P, and Vendruscolo M.
Int. J. Mol. Sci. 19, 1443 (2018) doi: 10.3390/ijms19051443
2017
Delivery of native proteins into C. elegans using a transduction protocol based on lipid vesicles
Perni M, Aprile FA*, Casford S, Mannini B, Sormanni P, Dobson CM, and Vendruscolo M*.
Sci. Rep. 7, 15045 (2017) doi: 10.1038/s41598-017-13755-9.
The polyglutamine protein ataxin-3 enables normal growth under heat shock conditions in the methylotrophic yeast Pichia pastoris
Bonanomi M, Roffia V, De Palma A, Lombardi A, Aprile FA, Visentin C, Tortora P, Mauri P, and Regonesi ME.
Sci. Rep. 7, 13417 (2017) doi: 10.1038/s41598-017-13814-1
Sequence specificity in the entropy-driven binding of a small molecule and a disordered peptide
Heller GT, Aprile FA, Bonomi M, Camilloni C, De Simone A, and Vendruscolo M.
J. Mol. Biol. 429, 2772-2779 (2017) doi: 10.1016/j.jmb.2017.07.016
The molecular chaperones DNAJB6 and Hsp70 cooperate to suppress alpha-synuclein aggregation
Aprile FA, Källstig E, Limorenko G, Vendruscolo M, Ron D, and Hansen C.
Sci. Rep. 7, 9039 (2017) doi: 10.1038/s41598-017-08324-z
Post-expression regioselective mutagenesis reveals a water bridged cysteine–cysteine redox regulation mechanism in bacterial protein tyrosine phosphatases
Bertoldo JB, Rodrigues T, Dunsmore L, Aprile FA, Marques MC, Rosado L, Boutureira O, Steinbrecher TB, Sherman W, Corzana F, Terenzi H, and Bernardes GJL.
Chem 3, 665–677 (2017) doi: 10.1016/j.chempr.2017.07.009
Selective targeting of primary and secondary nucleation pathways in Aβ42 aggregation using a rational antibody scanning method
Aprile FA, Sormanni P, Perni M, Arosio P, Linse S, Knowles TPJ, Dobson CM, and Vendruscolo M.
Sci. Adv. 3, e1700488 (2017) doi: 10.1126/sciadv.1700488
Methods of probing the interactions between small molecules and disordered proteins
Heller GT, Aprile FA, and Vendruscolo M.
Cell Mol Life Sci. 74, 3225–3243 (2017) doi: 10.1007/s00018-017-2563-41
Identification of a Pol III-associated regulator of small non-coding RNAs that is linked with disease-associated protein aggregation
Sin O, de Jong T, Mata-Cabana A, Kudron M, Zaini A, Aprile FA, Seinstra R, Stroo E, Prins RW, Martineau C, Wang HH, Hogewerf W, Steinhof A, Wanker EE, Vendruscolo M, Calkhoven CF, Reinke V, Guryev V, and Nollen EAA.
Mol. Cell 65, 1096-1108.e6 (2017) doi: 10.1016/j.molcel.2017.02.022
Inhibition of α-synuclein fibril elongation by hsp70 is governed by a kinetic binding competition between α-synuclein species
Aprile FA, Arosio P, Fusco G, Chen SW, Kumita JR, Dhulesia A, Tortora P, Knowles TPJ, and Vendruscolo M, Dobson CM, and Cremades N.
Biochemistry 56, 1177-1180 (2017) doi: 10.1021/acs.biochem.6b01178
A natural product inhibits the initiation of α-synuclein aggregation by displacing it from lipid membranes and suppresses its toxicity
Perni M, Galvagnion C, Alexander SM, Meisl G, Müller MBD, Challa PK, Kirkegaard JB, Flagmeier P, Cohen SIA, Cascella R, Chen SW, Limbocker R, Sormanni P, Heller GT, Aprile FA, Cremades N, Cecchi C, Chiti F, Nollen EAA, Knowles TPJ, Vendruscolo M, Bax A, Zasloff M, and Dobson CM.
Proc Natl Acad Sci U S A 114, E1009-E1017 (2017) doi: 10.1073/pnas.1610586114
2016
Structure of a low-population binding intermediate in protein-RNA recognition
Borkar AN, Bardaro MF, Camilloni C, Aprile FA, Varani G, and Vendruscolo M.
Proc Natl Acad Sci U S A 113, 7171–7176 (2016) doi: 10.1073/pnas.1521349113
A microfluidic diffusion viscometer for rapid analysis of complex solutions
Arosio P, Hu K, Aprile FA, Müller T, and Knowles TPJ.
Anal. Chem. 88, 3488–3493 (2016) doi: 10.1021/acs.analchem.5b02930
Microfluidic diffusion analysis of the sizes and interactions of proteins under native solution conditions
Arosio P, Muller T, Rajah L, Yates EV, Aprile FA, Zhang Y, Cohen SIA, White DA, Herling TW, De Genst E, Linse S, Vendruscolo M, Dobson CM, and Knowles TPJ.
ACS Nano 10, 333–341 (2016) doi: 10.1021/acsnano.5b04713
2015
Biophysical approaches for the study of interactions between molecular chaperones and protein aggregates
Wright MA, Aprile FA, Arosio P, Vendruscolo M, Dobson CM, and Knowles TPJ.
Chem. Comm. 51, 14425-14234 (2015) doi: 10.1039/c5cc03689e
A rational design strategy for the selective activity enhancement of a molecular chaperone towards a target substrate
Aprile FA, Sormanni P, and Vendruscolo M.
Biochemistry 54, 5103-5112 (2015) doi: 10.1021/acs.biochem.5b00459
Cell surface localised Hsp70 is a cancer specific regulator of clathrin-independent endocytosis
Nimmervoll B, Chtcheglova LA, Juhasz K, Cremades N, Aprile FA, Sonnleitner A, Hinterdorfer P, Vigh L, Preiner J, and Balogi Z.
FEBS L. 589, 2747-2753 (2015) doi: 10.1016/j.febslet.2015.07.037
Rational design of antibodies targeting specific epitopes within intrinsically disordered proteins
Sormanni P*, Aprile FA*, and Vendruscolo M.
Proc. Natl. Acad. Sci. USA 112, 9902-9907 (2015) doi: 10.1073/pnas.1422401112
Structural characterization of toxic oligomers trapped during α-synuclein fibril formation
Chen SW, Drakulic S, Deas E, Ouberai M, Aprile FA, Arranz R, Ness S, Roodveldt C, Guilliams T, De-Genst EJ, Klenerman D, Wood NW, Knowles TPj, Alfonso C, Rivas G, Abramov AY, Valpuesta JM, Dobson CM, and Cremades N.
Proc Natl Acad Sci U S A 112, E1994-2003 (2015) doi: 10.1073/pnas.1421204112
Structure of a low-population intermediate state in the release of an enzyme product
De Simone A, Aprile FA, Dhulesia A, Dobson CM, and Vendruscolo M.
eLife 4, e02777 (2015) doi: 10.7554/eLife.02777
The structure and dynamics of the lymphocyte function associated antigen-1 I-domain in the inactive state underlie its inside-out/outside-in signalling and allosteric mechanism
Kukic P, Alvin Leung HT, Bemporad F, Aprile FA, Kumita JR, De Simone A, Camilloni C, and Vendruscolo M.
Structure 23, 745-753 (2015) doi: 10.1016/j.str.2014.12.020
The CamSol method of rational design of protein mutants with enhanced solubility
Sormanni P*, Aprile FA*, and Vendruscolo M.
J. Mol. Biol. 427, 478-490 (2015) doi: 10.1016/j.jmb.2014.09.02
2014
NMR characterization of the conformational fluctuations of the human lymphocyte function-associated antigen-1 I-domain
Leung HT, Kukic P, Camilloni C, Bemporad F, De Simone A, Aprile FA, Kumita JR, and Vendruscolo M.
Protein Sci. 23, 1596-1606 (2014) doi: 10.1002/pro.2538
2013
Hsp70 oligomerization is mediated by an interaction between the interdomain linker and the substrate-binding domain
Aprile FA, Dhulesia A, Stengel F, Roodveldt C, Benesch JL, Tortora P, Robinson CV, Salvatella X, Dobson CM, and Cremades N.
PLoS One 8, e67961 (2013) doi: 10.1371/journal.pone.0067961
Nanobodies raised against monomeric α-synuclein distinguish between fibrils at different maturation stages
Guilliams T, El-Turk F, Buell AK, O'Day EM, Aprile FA, Esbjörner EK, Vendruscolo M, Cremades N, Pardon E, Wyns L, Welland ME, Steyaert J, Christodoulou J, Dobson CM, and De Genst E.
J. Mol. Biol. 425, 2397-2411 (2013) doi: 10.1016/j.jmb.2013.01.040
2012
The relationship between aggregation and toxicity of polyglutamine-containing ataxin-3 in the intracellular environment of Escherichia coli
Invernizzi G*, Aprile FA*, Natalello A, Ghisleni A, Penco A, Relini A, Doglia SM, Tortora P, and Regonesi ME.
PLoS One 7, e51890 (2012) doi: 0.1371/journal.pone.0051890
*Authors equally contributed to the work
Direct observation of the interconversion of normal and toxic forms of α-synuclein
Cremades N, Cohen SI, Deas E, Abramov AY, Chen AY, Orte A, Sandal M, Clarke RW, Dunne P, Aprile FA, Bertoncini CW, Wood NW, Knowles TPJ, Dobson CM, and Klenerman D.
Cell 149, 1048-1059 (2012) doi: 10.1016/j.cell.2012.03.037