Fluorescence analysis of the action of soluble derivatives of fullerene C60 on amyloid fibrils of the brain peptide Aβ(1–42)

AbstractPathological aggregation of the protein tau into insoluble aggregates is a hallmark of neurodegenerative diseases. The emergence of disease-specific tau aggregate structures termed tau strains, however, remains elusive. Here we show that full-length tau protein can be aggregated in the absence of co-factors into seeding-competent amyloid fibrils that sequester RNA. Using a combination of solid-state NMR spectroscopy and biochemical experiments we demonstrate that the co-factor-free amyloid fibrils of tau have a rigid core that is similar in size and location to the rigid core of tau fibrils purified from the brain of patients with corticobasal degeneration. In addition, we demonstrate that the N-terminal 30 residues of tau are immobilized during fibril formation, in agreement with the presence of an N-terminal epitope that is specifically detected by antibodies in pathological tau. Experiments in vitro and in biosensor cells further established that co-factor-free tau fibrils efficiently seed tau aggregation, while binding studies with different RNAs show that the co-factor-free tau fibrils strongly sequester RNA. Taken together the study provides a critical advance to reveal the molecular factors that guide aggregation towards disease-specific tau strains.

Download Full-text

Surface enhanced Raman scattering detection of water-soluble derivatives of fullerene C60 and their covalent conjugates with dyes in biological model systems

Doklady Physical Chemistry ◽

10.1134/s0012501616010073 ◽

2016 ◽

Vol 466 (1) ◽

pp. 23-27

Author(s):

D. A. Poletaeva ◽

A. Yu. Rybkin ◽

V. I. Kukushkin ◽

A. Yu. Belik ◽

N. S. Goryachev ◽

...

Keyword(s):

Raman Scattering ◽

Fullerene C60 ◽

Water Soluble ◽

Model Systems ◽

Biological Model ◽

Surface Enhanced ◽

Surface Enhanced Raman ◽

Enhanced Raman Scattering ◽

Derivatives Of ◽

Covalent Conjugates

Download Full-text

ChemInform Abstract: Novel π-Conjugated Systems: The First Silatropylium Ion and Planar Cyclooctatetraene Anellated with Bicyclic Frameworks and New Derivatives of Fullerene C60

ChemInform ◽

10.1002/chin.200220247 ◽

2010 ◽

Vol 33 (20) ◽

pp. no-no

Author(s):

Koichi Komatsu ◽

Tohru Nishinaga ◽

Yasujiro Murata ◽

Akira Matsuura ◽

Yoshiteru Izukawa ◽

...

Keyword(s):

Fullerene C60 ◽

Conjugated Systems ◽

Derivatives Of

Download Full-text

Synaptic vesicle mimics affect the aggregation of wild-type and A53T α-synuclein variants differently albeit similar membrane affinity

Protein Engineering Design and Selection ◽

10.1093/protein/gzz021 ◽

2019 ◽

Vol 32 (2) ◽

pp. 59-66

Author(s):

Sandra Rocha ◽

Ranjeet Kumar ◽

Istvan Horvath ◽

Pernilla Wittung-Stafshede

Keyword(s):

Synaptic Vesicles ◽

Amyloid Fibrils ◽

Membrane Surface ◽

Amyloid Formation ◽

Wild Type ◽

Membrane Affinity ◽

Axis Parallel ◽

Biophysical Techniques ◽

Small Unilamellar Vesicles ◽

The Brain

Abstract α-Synuclein misfolding results in the accumulation of amyloid fibrils in Parkinson’s disease. Missense protein mutations (e.g. A53T) have been linked to early onset disease. Although α-synuclein interacts with synaptic vesicles in the brain, it is not clear what role they play in the protein aggregation process. Here, we compare the effect of small unilamellar vesicles (lipid composition similar to synaptic vesicles) on wild-type (WT) and A53T α-synuclein aggregation. Using biophysical techniques, we reveal that binding affinity to the vesicles is similar for the two proteins, and both interact with the helix long axis parallel to the membrane surface. Still, the vesicles affect the aggregation of the variants differently: effects on secondary processes such as fragmentation dominate for WT, whereas for A53T, fibril elongation is mostly affected. We speculate that vesicle interactions with aggregate intermediate species, in addition to monomer binding, vary between WT and A53T, resulting in different consequences for amyloid formation.

Download Full-text

New Plant Growth Stimulants Based on Water-Soluble Nanoparticles of N-Substituted Monoamino-Acid Derivatives of Fullerene C60 and the Study of their Mechanisms of Action

BIOPHYSICS ◽

10.1134/s0006350920040272 ◽

2020 ◽

Vol 65 (4) ◽

pp. 635-641

Author(s):

V. A. Volkov ◽

O. V. Yamskova ◽

M. V. Voronkov ◽

D. V. Kurilov ◽

V. S. Romanova ◽

...

Keyword(s):

Plant Growth ◽

Mechanisms Of Action ◽

Fullerene C60 ◽

Water Soluble ◽

Plant Growth Stimulants ◽

Derivatives Of

Download Full-text

Parkinson’s disease is a type of amyloidosis featuring accumulation of amyloid fibrils of α-synuclein

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1906124116 ◽

2019 ◽

Vol 116 (36) ◽

pp. 17963-17969 ◽

Cited By ~ 24

Author(s):

Katsuya Araki ◽

Naoto Yagi ◽

Koki Aoyama ◽

Chi-Jing Choong ◽

Hideki Hayakawa ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Amyloid Fibrils ◽

Lewy Bodies ◽

X Ray Diffraction ◽

Thin Sections ◽

X Ray ◽

Β Sheet ◽

The Brain

Many neurodegenerative diseases are characterized by the accumulation of abnormal protein aggregates in the brain. In Parkinson’s disease (PD), α-synuclein (α-syn) forms such aggregates called Lewy bodies (LBs). Recently, it has been reported that aggregates of α-syn with a cross-β structure are capable of propagating within the brain in a prionlike manner. However, the presence of cross-β sheet-rich aggregates in LBs has not been experimentally demonstrated so far. Here, we examined LBs in thin sections of autopsy brains of patients with PD using microbeam X-ray diffraction (XRD) and found that some of them gave a diffraction pattern typical of a cross-β structure. This result confirms that LBs in the brain of PD patients contain amyloid fibrils with a cross-β structure and supports the validity of in vitro propagation experiments using artificially formed amyloid fibrils of α-syn. Notably, our finding supports the concept that PD is a type of amyloidosis, a disease featuring the accumulation of amyloid fibrils of α-syn.

Download Full-text

Conversion of ethanolamine, monomethylethanolamine and dimethylethanolamine to choline-containing compounds by neurons in culture and by the rat brain

Biochemical Journal ◽

10.1042/bj2640555 ◽

1989 ◽

Vol 264 (2) ◽

pp. 555-562 ◽

Cited By ~ 26

Author(s):

C Andriamampandry ◽

L Freysz ◽

J N Kanfer ◽

H Dreyfus ◽

R Massarelli

Keyword(s):

Rat Brain ◽

Primary Culture ◽

De Novo ◽

Water Soluble ◽

Intraventricular Injection ◽

Chick Embryos ◽

Fetal Rat ◽

Derivatives Of ◽

The Brain

The incubation of neurons from chick embryos in primary culture with [3H]ethanolamine revealed the conversion of this base into monomethyl, dimethyl and choline derivatives, including the corresponding free bases. Labelling with [methyl-3H]monomethylethanolamine and [methyl-3H]dimethylethanolamine supported the conclusion that in chick neuron cultures, phosphoethanolamine appears to be the preferential substrate for methylation, rather than ethanolamine or phosphatidylethanolamine. The methylation of the latter two compounds, in particular that of phosphatidylethanolamine, was seemingly stopped at the level of their monomethyl derivatives. Fetal rat neurons in primary culture incubated with [3H]ethanolamine showed similar results to those observed with chick neurones. However, phosphoethanolamine and phosphatidylethanolamine and, to a lesser extent, free ethanolamine, appeared to be possible substrates for methylation reactions. The methylation of water-soluble ethanolamine compounds de novo was further confirmed by experiments performed in vivo by intraventricular injection of [3H]ethanolamine. Phosphocholine and the monomethyl and dimethyl derivatives of ethanolamine were detected in the brain 15 min after injection.

Download Full-text