2024.11.11
Journal of Biological Chemistry
Different charged biopolymers induce α-synuclein to form fibrils with distinct structures
This research offers valuable insights into how various charged biopolymers affect the aggregation process and the resultant structures of α-Syn fibrils, thereby enhancing our understanding of the structural variations in α-Syn fibrils across different pathological conditions.
More
2024.10.17
Nature Structural & Molecular Biology
Time-course remodeling and pathology intervention of α-synuclein amyloid fibril by heparin and heparin-like oligosaccharides
This study reveals that heparin polysaccharides bind to α-synuclein fibrils, remodel their structure, and play a role in disease progression. It pioneers using bioactive oligosaccharides to regulate protein aggregation and toxicity, offering new strategies for drug development targeting neurodegenerative disease aggregates.
More
2024.9.27
Journal of the American Chemical Society
Inhibitor development for α-synuclein fibril's disordered region to alleviate Parkinson's disease pathology
This study designs the first small molecules targeting the disordered region of α-synuclein fibrils, blocking their interaction with cell receptors to inhibit propagation and neuroinflammation, and providing new strategies for Parkinson's disease treatment.
More
2024.8.22
PNAS
Binding adaptability of chemical ligands to polymorphic α-synuclein amyloid fibrils
This study investigated the interactions of small molecules belonging to four distinct scaffolds, with different α-Syn fibril polymorphs. Using cryo-electron microscopy, we determined the structures of these molecules when bound to the fibrils formed by E46K mutant α-Syn and compared them to those bound with wild-type α-syn fibrils.
More
2024.5.25
National Science Review
Lysophosphatidylcholine binds α-synuclein and prevents its pathological aggregation
This work underscores the critical role of LPLs in preserving the natural conformation of α-syn to inhibit improper aggregation, and establishes a potential connection between lipid metabolic dysfunction and α-Syn aggregation in PD.
More
2023.7.7
Cell
Development of an α-synuclein positron emission tomography tracer for imaging synucleinopathies
This study identifies a brain-permeable, rapid-washout PET tracer [18F]-F0502B and resolves its 2.8 Å atomic structure in complex with α-Syn fibrils. PET imaging demonstrates its selective detection of α-Syn aggregates in mouse and non-human primate PD models, offering a novel tool for early Parkinson's disease diagnosis.
More
2023.7.3
Nature Chemical Biology
Structural mechanism for specific binding of chemical compounds to amyloid fibrils
This study employs cryo-electron microscopy (cryo-EM) to systematically elucidate the structural landscape of amyloid fibril interactions with a diverse panel of compounds, including classic dyes, (pre)clinically imaging tracers and newly identified binders from high-throughput screening. This study holds significant implications for the development of new diagnostic and therapeutic approaches for neurodegenerative diseases.
More
2023.2.16
Journal of the American Chemical Society
Conformational dynamics of an α-synuclein fibril upon receptor binding revealed by insensitive nuclei enhanced by polarization transfer-based solid-state nuclear magnetic resonance and cryo-electron microscopy
This study deciphers how LAG3 binds to α-Syn fibrils' terminal domains, triggering core region remodeling at atomic resolution.
More
2022.9.20
Cell Reports
Interaction of RAGE with α-synuclein fibrils mediates inflammatory response of microglia
This study reveals that pathological α-Syn fibrils induce microglial inflammatory responses by directly binding to the RAGE receptor on the cell surface. It also elucidates the molecular mechanism of RAGE recognition of α-Syn fibrils. This work provides a potential new therapeutic target for Parkinson's disease (PD) by inhibiting neuroinflammation.
More
2021.5.25
PNAS
Mechanistic basis for receptor-mediated pathological α-synuclein fibril cell-to-cell transmission in Parkinson's disease
This work reveals the important role of post-translational modification in cell-to-cell transmission of α-Syn pathological fibrils in inducing pathological toxicity, and provides new ideas for the development of PD drugs.
More
