Polyamine Biology

Summary:

Polyamines (PA) remain essential for growth, and interact with a variety of macromolecules, both electrostatically and covalently promoting different cellular effects. Polyamines carry positive charges (+2, +3, +4) on nitrogen at physiological pH and become “supercations”; yet they distribute the charge along the entire length of the carbon chain making them unique and distinct from point-charges of other cellular bivalent cations. This intrinsically changes protein, DNA, RNA, and macromolecule folding dynamics. Our lab showed that bioactive polyamines directly block tau’s aggregation and can promote microtubule assembly, but inactive acetylated polyamines fail to mimic this affect. We demonstrated the ability of physiological concentrations of “natural endogenous molecules” (polyamines) to inhibit the oligomerization/ aggregation of tau and could have widespread applications because of tau’s ability to seed and promote the spread from one region of the brain to another. Polyamines may interact differently with various tau strains. We know that certain stressors including physical or emotional and diseases including AD and other tauopathies mount a polyamine stress response (PSR). Depending on the type of PSR (i.e. either promoting anabolism or catabolism) this can create a flux in polyamines and their acetylated metabolites to create a feed forward cycle of disease progression that can impact behavior.