Nanostructural Modulation of G-Quadruplex DNA in Neurodegeneration: Orotate Interaction Revealed Through Experimental and Computational Approaches.

ABSTRACT: The natural compound orotic acid and its anionic form, orotate, play a pivotal role in various biological processes, serving as essential intermediates in pyrimidine de novo synthesis, with demonstrated connections to dietary, supplement, and neurodrug applications. A novel perspective on biomolecular aggregation at the nanoscale, particularly pertinent to neurodegeneration, challenges the established paradigm positing that peptide (amyloid beta) and protein (tau) aggregation mainly govern the molecular events underlying prevalent neuropathologies. Emerging biological evidence indicates a notable role for G-quadruplex (G4) DNA aggregation in neurodegenerative processes affecting neuronal cells, particularly in the presence of extended (G₄C₂)_n repeats in nuc

SUBMITTER: Falanga AP 

PROVIDER: S-EPMC11744338 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature