Inhibition of Tau amyloid fibril formation by folic acid: In-vitro and theoretical studies.

ABSTRACT

Tauopathy belongs to a various class of neurodegenerative diseases in which insoluble Tau aggregates are formed, and cellular function is lost, leading to neuronal death. Various therapeutic strategies have been investigated, and many drugs have been proposed as a cure for these diseases but their toxicity and adverse side effects, limit their consumption by humans. Alternatively, the use of non-toxic medicine without any adverse or undesirable secondary effects like nutrients, vitamins, as well as herbal and mineral supplements is common and continues to increase each year. Folic acid is a form of vitamin B and plays a vital role in the synthesis of nucleic acid, methionine regeneration, and in shuttling one-carbon units essential for normal cell division and growth. We investigated the interaction between folic acid and Tau protein, then experimental and theoretical evidence were provided for the suppressing effects of folic acid on Tau fibril formation. The obtained results showed that folic acid could interact with Tau through a spontaneous binding process, mainly by hydrophobic forces, and this interaction leads to a decline in protein-protein interactions through stabilizing its native state, limiting successful Tau-seed oligomerization and consequently decelerating polymerization of Tau amyloid aggregates.