A Potential Role of Natural Bioactive Compounds Found in Food in the Prevention of Idiopathic Parkinson's Disease.

Various clinical studies aimed at modifying the progression of idiopathic Parkinson's disease have been unsuccessful. Similarly, several nutritional trials using bioactive compounds have shown positive effects for patients but have also failed to slow or reduce the disease's progression. This repeated failure is likely because these studies ignore the extremely slow neurodegenerative process, which unfolds over many years. The molecular mechanism behind the loss of neuromelanin-containing dopaminergic neurons in the nigrostriatal system in idiopathic Parkinson's disease remains unclear. This is a conceptual/theoretical review based mainly on mechanistic and preclinical evidence, with no direct clinical data. However, research suggests that aminochrome, an endogenous neurotoxin, may trigger the degeneration of these neurons through a single-neuron degeneration model. In this model, aminochrome selectively destroys individual neurons without spreading to neighboring cells. Aminochrome is produced during neuromelanin synthesis, a process that is normally harmless because protective enzymes like DT-diaphorase and glutathione transferase M2-2 neutralize aminochrome's neurotoxic effects. Increasing the levels of these enzymes could offer neuroprotection. The KEAP1/NRF2 signaling pathway is critical for regulating antioxidant enzymes, such as DT-diaphorase and glutathione transferase M2-2. Importantly, specific bioactive compounds from food can activate this pathway, increasing the production of these protective enzymes. For instance, the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), along with astaxanthin-a compound present in cold-water fish like salmon-have been demonstrated to enhance enzyme expression. This connection leads to a compelling question: Could dietary interventions help prevent idiopathic Parkinson's disease? Answering this will require further research.