Nanorod-associated plasmonic circular dichroism monitors the handedness and composition of ?-synuclein fibrils from Parkinson?s disease models and post-mortem brain
Year: 2024
Authors: Longhena F., Boujebene R., Brembati V., Sandre M., Bubacco L., Abbate S., Longhi G., Bellucci A.
Autors Affiliation: Univ Brescia, Dept Mol & Translat Med, Viale Europa 11, I-25123 Brescia, Italy; Univ Cambridge, Dept Clin Neurosci, Clifford Allbutt Bldg,Hills Rd, Cambridge CB2 0AH, England; Univ Padua, Dept Biol, Via Ugo Bassi 58b, I-35121 Padua, Italy; INO CNR, Ist Nazl Ottica, CSMT, Res Unit Brescia, Via Branze 35, I-25123 Brescia, Italy.
Abstract: Human full-length (fl) alpha Syn fibrils, key neuropathological hallmarks of Parkinson’s disease (PD), generate intense optical activity corresponding to the surface plasmon resonance of interacting gold nanorods. Herein, we analysed fibril-enriched protein extracts from mouse and human brain samples as well as from SK-N-SH cell lines with or without human fl and C-terminally truncated (Ctt) alpha Syn overexpression and exposed them to alpha Syn monomers, recombinant fl alpha Syn fibrils or Ctt alpha Syn fibrils. In vitro-generated human recombinant fl and Ctt alpha Syn fibrils and fibrils purified from SK-N-SH cells with fl or Ctt alpha Syn overexpression were also analysed using transmission electron microscopy (TEM) to gain insights into the nanorod-fibril complexes. We found that under the same experimental conditions, bisignate circular dichroism (CD) spectra of Ctt alpha Syn fibrils exhibited a blue-wavelength shift compared to that of fl alpha Syn fibrils. TEM results supported that this could be attributed to the different properties of nanorods. In our experimental conditions, fibril-enriched PD brain extract broadened the longitudinal surface plasmonic band with a bisignate CD couplet centred corresponding to the absorption band maximum. Plasmonic CD (PCD) couplets of in vivo- and in vitro-generated fibrils displayed sign reversal, suggesting their opposite handedness. Moreover, the incubation of in vitro-generated human recombinant fl alpha Syn fibrils in mouse brain extracts from alpha Syn null mice resulted in PCD couplet inversion, indicating that the biological environment may shape the handedness of alpha Syn fibrils. These findings support that nanorod-based PCD can provide useful information on the composition and features of alpha Syn fibrils from biological materials. Nanorod-based plasmonic circular dichroism distinguishes the composition and features of different alpha Syn fibrils.
Journal/Review: NANOSCALE
More Information: RB, GL and SA thank the PhD school Molecular Genetics, Biotechnologies and Experimental Medicine in the University of Brescia, for supporting RB throughout her PhD studies. The Italian Ministry of University and Research (PRIN 2017 program 2017A4XRCA_003) is acknowledged for funding. AB is grateful to the Michael J. Fox Foundation for Parkinson’s disease, NY, USA (Target Advancement Program, grant ID #10742.01) and to the Italian MIUR PRIN 2017-1065.KeyWords: Transgenic Mouse Model; Conjugated Au Nanorods; Supramolecular Chirality; Polarized Luminescence; Photothermal Treatment; Metal Nanoparticles; Gold Nanoparticles; Optical-activity; Insulin Fibrils; Lewy BodiesDOI: 10.1039/d4nr03002hCitations: 1data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2024-11-17References taken from IsiWeb of Knowledge: (subscribers only)