Interplay between membrane dependent polymorphic a-synuclein fibril conformation and its cellular pathologies

The formation of α-syn aggregations, known as amyloid fibrils, is recognized as causing various neurodegenerative diseases, collectively referred to as synucleinopathies. Given its roles in the disease-specific propagation of α-syn pathology within synucleinopathies, it is important to understand how distinct forms of α-syn fibrils are observed despite their structural diversity. To fill this knowledge gap, our group aims to elucidate the molecular interactions between polymorphic α-syn fibrils and a range of cellular factors. This will provide structural insights into the development of disease-specific aggregation inhibitors and antibodies based on the structural specificities.

 

Lipid-driven amyloid-β aggregation and its interactions with lipid bilayers

Aβ oligomers are critical in initiating the process that leads to neuronal loss in Alzheimer’s disease. As fundamental components of cellular membranes, lipids play important roles both in mediating Aβ’s physiological and toxic functions in Alzheimer’s disease through interactions with various cellular membranes. Our research focuses on the study of Aβ-lipid complexes, biological forms of Aβ that interact with and damage neuronal membranes or synaptic vesicles, leading to the pathology of Alzheimer’s disease.