Co-aggregation of α-synuclein with amyloid-β stabilizes β-sheet-rich oligomers and enhances the formation of β-barrels
Literature Information
Fengjuan Huang, Yuying Liu, Ying Wang, Jia Xu, Jiangfang Lian, Yu Zou, Chuang Wang, Feng Ding
Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative diseases with markedly different pathological features of β-amyloid (Aβ) plaques and α-synuclein (αS) Lewy bodies (LBs), respectively. However, clinical overlaps in symptoms and pathologies between AD and PD are commonly observed caused by the cross-interaction between Aβ and αS. To uncover the molecular mechanisms behind their overlapping symptoms and pathologies, we computationally investigated the impact of αS on an Aβ monomer and dimerization using atomistic discrete molecular dynamics simulations (DMD). Our results revealed that αS could directly interact with Aβ monomers and dimers, thus forming β-sheet-rich oligomers, including potentially toxic β-barrel intermediates. The binding hotspot involved the second half of the N-terminal domain and NAC region in αS, along with residues 10–21 and 31–42 in Aβ. In their hetero-complex, the binding hotspot primarily assumed a β-sheet core buried inside, which was dynamically shielded by the highly charged, amyloid-resistant C-terminus of αS. Because the amyloid prion region was the same as the binding hotspot being buried, their fibrillization may be delayed, causing the toxic oligomers to increase. This study sheds light on the intricate relationship between Aβ and αS and provides insights into the overlapping pathology of AD and PD.
Related Literature
Exchange potentials for semi-classical electrons
Judith Herzfeld, Solen Ekesan
DOI: 10.1039/C6CP06100A
Infrared and fluorescence assessment of the hydration status of the tryptophan gate in the influenza A M2 proton channel
Beatrice N. Markiewicz, Thomas Lemmin, Wenkai Zhang, Ismail A. Ahmed, Hyunil Jo, Giacomo Fiorin, William F. DeGrado
DOI: 10.1039/C6CP03426H
Permselectivity and thickness-dependent ion transport properties of overoxidized polyaniline: a mechanistic investigation
Subrata Mondal, M. V. Sangaranarayanan
DOI: 10.1039/C6CP04975C
Correction: Ion collision cross section analyses in quadrupole ion traps using the filter diagonalization method: a theoretical study
Ting Jiang, Muyi He, Dan Guo, Yanbing Zhai
DOI: 10.1039/C6CP90248K
Extraordinary stability of hemocyanins from L. polyphemus and E. californicum studied using infrared spectroscopy from 294 to 20 K
Mireille Khalil, Zahia Boubegtiten-Fezoua, Nadja Hellmann, Petra Hellwig
DOI: 10.1039/C6CP03510H
Development of type-I/type-II hybrid dye sensitizer with both pyridyl group and catechol unit as anchoring group for type-I/type-II dye-sensitized solar cell
Yousuke Ooyama, Kensuke Furue, Toshiaki Enoki, Masahiro Kanda, Yohei Adachi, Joji Ohshita
DOI: 10.1039/C6CP06513A
A comparison of the experimental and theoretical charge density distributions in two polymorphic modifications of piroxicam
Felcia Lai, Jonathan J. Du, Linda Váradi, Daniel Baker, Paul W. Groundwater, Jacob Overgaard, James A. Platts, David E. Hibbs
DOI: 10.1039/C6CP02690G
125Te NMR provides evidence of autoassociation of organo-ditellurides in solution
P. J. W. Elder, I. Vargas-Baca
DOI: 10.1039/C6CP05892B
You might also like
Are there alternatives to 1-(4-Chlorophenyl)-N-hydroxymethanimine (CAS: 3848-36-0) in synthesis?
When considering alternatives to 1-(4-Chlorophenyl)-N-hydroxymethanimine (CAS: 3...
How should (1R,9S,10S,12S,14E,16S,19R,20R,21S,22R)-3,9,21-Trihydroxy-5,10,12,14,16,20,22-heptamethyl-23,24-dioxatetracyclo[17.3.1.1~6,9~.0~2,7~]tetracosa-2,5,7,14-tetraen-4-one (CAS: 183202-73-5) be stored?
This compound should be stored in a cool, dry place away from direct sunlight. I...
How is 3-(4-Bromophenyl)-5-(2-fluorophenyl)-1,2,4-oxadiazole (CAS: 419553-16-5) typically synthesized?
3-(4-Bromophenyl)-5-(2-fluorophenyl)-1,2,4-oxadiazole is synthesized through a m...
How is 5-Chloro-2-(4-chlorophenyl)-4-methyl-6-[3-(1-piperidinyl)propoxy]pyrimidine (CAS: 1639220-19-1) typically synthesized?
5-Chloro-2-(4-chlorophenyl)-4-methyl-6-[3-(1-piperidinyl)propoxy]pyrimidine (CAS...
What industries use 2-Chloro-4-(difluoromethoxy)pyridine (CAS: 1206978-15-5)?
2-Chloro-4-(difluoromethoxy)pyridine is used in the pharmaceutical industry for ...
What regulatory guidelines apply to 3-Chloro-6-methylpyridazine (CAS: 1121-79-5)?
3-Chloro-6-methylpyridazine (CAS: 1121-79-5) is classified under the Globally Ha...
Are there alternatives to Methyl 4,5-dimethyl-2-nitrobenzoate in synthesis?
Several alternatives can be used in the synthesis of Methyl 4,5-dimethyl-2-nitro...
Are there alternatives to (2E,2'E)-3,3'-(1,4-Phenylene)bisacrylaldehyde in synthesis?
Alternatives to (2E,2'E)-3,3'-(1,4-Phenylene)bisacrylaldehyde include other acry...
What is 3-Amino-5-chloropyridin-2-ol hydrochloride (CAS: 1261906-29-9)?
3-Amino-5-chloropyridin-2-ol hydrochloride is an organic compound with the CAS n...
What precautions should be taken when handling 6,7-Difluoro-2,3-dihydro-4H-chromen-4-one (CAS: 1092349-93-3)?
When handling 6,7-Difluoro-2,3-dihydro-4H-chromen-4-one, it is essential to wear...
Source Journal
Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.














