{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T13:35:07Z","timestamp":1783431307681,"version":"3.54.6"},"reference-count":119,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Various clinical studies aimed at modifying the progression of idiopathic Parkinson\u2019s 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\u2019s 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\u2019s 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\u2019s 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\u2014a compound present in cold-water fish like salmon\u2014have been demonstrated to enhance enzyme expression. This connection leads to a compelling question: Could dietary interventions help prevent idiopathic Parkinson\u2019s disease? Answering this will require further research.<\/jats:p>","DOI":"10.3390\/nu17213376","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:59:36Z","timestamp":1761659976000},"page":"3376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Potential Role of Natural Bioactive Compounds Found in Food in the Prevention of Idiopathic Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"17","author":[{"given":"Sandro","family":"Huenchuguala","sequence":"first","affiliation":[{"name":"Escuela de Tecnolog\u00eda M\u00e9dica, Facultad de Salud, Universidad Santo Tom\u00e1s, Santiago 8370003, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-673X","authenticated-orcid":false,"given":"Juan","family":"Segura-Aguilar","sequence":"additional","affiliation":[{"name":"Molecular & Clinical Pharmacology, Instituto de Ciencias Biom\u00e9dicas (ICBM), Faculty of Medicine, University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrneurol.2014.226","article-title":"The ongoing pursuit of neuroprotective therapies in Parkinson disease","volume":"11","author":"Athauda","year":"2015","journal-title":"Nat. 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