Insight
In misfolding diseases, amyloidogenic proteins form large aggregates, which can be toxic to neuronal cells, leading to the disease state. In vitro experiments have shown that amyloid aggregates with other amyloids of the same type. However, recent discoveries in neurodegeneration and aging have revealed that amyloid can also co-aggregate with biomolecules present in high concentrations in the cytosols. Therefore, it is crucial to adopt a panoramic perspective (MetaView) and examine mixed states (MetaStable), where various forms of aggregates combine with different biomolecules. We refer to these aggregates as “MetaAggregates,” and our research aims to understand how they are formed. Once this process is clarified, we will use it as a blueprint to develop inhibitors with minimal adverse effects, focusing on small molecules and nucleic acid medicines.
Grand Plan
A01:[Amyloid and heteroamyloid] Formation of meta-aggregates and their toxicity in mixed dementia
Kenjiro Ono
Graduate School of Medical Sciences, Kanazawa University. Professor
A02:[Amyloid and nucleic acid structure] The formation and propagation of meta-aggregates by RNA phase transition
Yasushi Yabuki
Institute of Molecular Embryology and Genetics, Kumamoto university. Assistant Professor
A03:[Amyloid and protein] Comprehensive search and validation of meta-aggregates by molecular evolutionary method
Kazuma Murakami
Graduate School of Agriculture, Kyoto University. Associate Professor
B01:Observation of structural dynamics of meta-aggregates
Takahiro Nakayama
Nano Life Science Institute, Kanazawa University. Associate Professor