On the Potential Role of Phytate Against Neurodegeneration: It Protects Against Fe3+-Catalyzed Degradation of Dopamine and Ascorbate, and Against Fe3+-Induced Protein Aggregation

Myo-inositol-1,2,3,4,5,6-hexakisphosphate (IP6), commonly found in plant-derived foods, has important pharmacological properties against many pathological processes. One of them could be the neurodegeneration, stimulated by a dysregulated metal metabolism. Consequently, we explore here the role of IP6 in mitigating neurodegenerative processes catalyzed by dysregulated free iron. Using dopamine and ascorbic acid as models of neuronal redox systems, we demonstrate that IP6 effectively chelates Fe³⁺, inhibiting its ability to catalyse the oxidative degradation of DA and AA. Our findings reveal that IP6 prevents the formation of harmful intermediates such as neuromelanin and reactive oxygen species, which are associated with neuronal damage. Furthermore, we examined the effect of IP6 on Fe³⁺-induced protein aggregation, focusing on α-synuclein, a protein directly linked to Parkinson's disease. IP6 altered the aggregation mechanism of αS by accelerating the conversion of toxic oligomers into less harmful amyloid fibrils, thus reducing the potential for neuronal damage. Our results highlight the dual function of IP6 as potent Fe³⁺ chelator and modulator of protein aggregation pathways, thus emphasizing its potential as a neuroprotective agent. Consequently, IP6 offers promising therapeutic features for mitigating the progression of neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases.