Article ; Online: Structure specific neuro-toxicity of α-synuclein oligomer.
International journal of biological macromolecules
2023 Volume 253, Issue Pt 1, Page(s) 126683
Abstract: Parkinson's disease (PD) is linked to α-synuclein (aS) aggregation and deposition of amyloid in the substantia nigra region of the brain tissues. In the current investigation we produced two distinct classes of aS oligomer of differed protein ... ...
Abstract | Parkinson's disease (PD) is linked to α-synuclein (aS) aggregation and deposition of amyloid in the substantia nigra region of the brain tissues. In the current investigation we produced two distinct classes of aS oligomer of differed protein conformation, stability and compared their toxic nature to cultured neuronal cells. Lyophilized oligomer (LO) was produced in storage of aS at-20 °C for 7 days and it was enriched with loosely hold molten globule like structure with residues having preferences for α-helical conformational space. The size of the oligomer was 4-5.5 nm under AFM. This kind of oligomer exhibited potential toxicity towards neuronal cell lines and did not transform into compact β-sheet rich amyloid fiber even after incubation at 37 °C for several days. Formation of another type of oligomer was often observed in the lag phase of aS fibrillation that often occurred at an elevated temperature (37 °C). This kind of heat induced oligomer (IO) was more hydrophobic and relatively less toxic to neuronal cells compared to lyophilized oligomer (LO). Importantly, initiation of hydrophobic zipping of aS caused the transformation of IO into thermodynamically stable β-sheet rich amyloid fibril. On the other hand, the presence of molten globule like conformation in LO, rendered greater toxicity to cultured neuronal cells. |
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MeSH term(s) | Humans ; alpha-Synuclein/chemistry ; Parkinson Disease/metabolism ; Protein Conformation ; Neurons/metabolism ; Protein Conformation, beta-Strand ; Amyloid/chemistry ; Amyloidogenic Proteins |
Chemical Substances | alpha-Synuclein ; Amyloid ; Amyloidogenic Proteins |
Language | English |
Publishing date | 2023-09-04 |
Publishing country | Netherlands |
Document type | Journal Article |
ZDB-ID | 282732-3 |
ISSN | 1879-0003 ; 0141-8130 |
ISSN (online) | 1879-0003 |
ISSN | 0141-8130 |
DOI | 10.1016/j.ijbiomac.2023.126683 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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