3. Conclusions
The Aβ42 monomer and oligomer structures in aqueous solution are of high
importance as they initiate fibril formation and are believed to be the
most toxic species. While the community believes on random coil –
β-sheet oligomers and the role of β-hairpin82 in the
early steps of aggregation, the existence of α-helical bundle metastable
intermediates of Aβ42 oligomers is rarely cited, while it is predicted
by AlphaFold2 and is, more importantly, supported indirectly by a large
number of experimental studies on Aβ and many amyloid polypeptides under
various conditions. It is important to note that there is a general
resistance of the field to believing CD in detecting α-helix in
aggregates, because of light-scattering interference and skewing of the
CD spectrum. But the α-helix signal in oligomers was further evidenced
by FTIR and Raman spectroscopies in addition to CD. Clearly, the
coexistence of α-rich oligomers and β-rich oligomers en route to fibril
formation has to be considered when designing drugs targeting Aβ
monomers and oligomers.76,81,83,84
AUTHOR INFORMATION
Corresponding Author
E-mail: philippe.derreumaux@ibpc.fr
ORCID:
Derreumaux: 0000-0001-9110-5585
Sterpone: 0000-0003-0894-8069,
fabio.sterpone@ibpc.fr
Nguyen: 0000-0003-1284-967X, Phuong.nguyen@ibpc.fr
Notes. The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by the “Initiative d’Excellence” program from
the French State, Grant “DYNAMO”, ANR-11-LABX-0011. PD thanks Ronald
Wetzel for useful discussions and Geoffrey Letessier of the Laboratoire
de Biochimie Théorique for technical support.