RNA structures present a promising target for early intervention in Parkinson's disease

Originally published by Kumamoto University on November 1, 2024

The trigger for neurodegeneration is the assembly of G4 structures driven by increased intracellular calcium ions (Ca2+) due to cellular stress. α-Synuclein binds directly to G4, shifting into an aggregate-prone structure that employs G4 as a scaffold to form harmful clusters. Therefore, inhibiting G4 assembly can prevent α-synuclein aggregation, helping to protect against neuronal function loss. Credit: Cell (2024). DOI: 10.1016/j.cell.2024.09.037

A team of researchers at Kumamoto University has uncovered a mechanism in the formation of harmful protein aggregates that lead to neurodegenerative diseases such as Parkinson's disease.

The team, led by Professor Norifumi Shioda and Associate Professor Yasushi Yabuki, identified for the first time that unique RNA structures called G-quadruplexes (G4s) play a central role in promoting the aggregation of α-synuclein, a protein associated with neurodegeneration.

The study is published in the journal Cell.

By demonstrating that inhibiting G4 assembly could potentially prevent the onset of synucleinopathies, this discovery positions G4 as a promising target for early intervention in these diseases.

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