Role of Polyphosphate in Amyloidogenic Processes

Polyphosphate (polyP), an extremely simple polyanion, has long been known to be involved in a variety of different cellular processes, ranging from stress resistance, biofilm formation, and virulence in bacteria to bone mineralization, blood clotting, and mammalian target of rapamycin (mTOR) signaling in mammalian organisms. Our laboratory recently discovered a completely unexpected role of polyP as a stabilizing scaffold for β-sheet-containing protein-folding intermediates. This realization led us to investigate the effects of polyP on amyloidogenic processes and the novel concept that polyP might play a role in neurodegenerative diseases. In this review, we will summarize recent results that show that polyP is a physiological modifier that accelerates amyloid fiber formation, alters fiber morphology, and protects cells against amyloid toxicity. We will review the current knowledge on the distribution, levels, and roles of polyP in the mammalian brain, and discuss potential mechanisms by which polyP might ameliorate amyloid toxicity.