{"title":"A Potential Role of Natural Bioactive Compounds Found in Food in the Prevention of Idiopathic Parkinson's Disease","authors":"Sandro Huenchuguala, Juan Segura‐Aguilar","doi":"10.20944/preprints202509.0025.v1","DOIUrl":null,"url":null,"abstract":"The molecular mechanism behind the loss of neuro-melanin-containing dopaminergic neurons in the nigrostriatal sys-tem in idiopathic Parkinson’s disease remains unclear. However, research suggests that aminochrome, an endogenous neurotoxin, may trigger the degeneration of these neurons through a sin-gle-neuron degeneration model. In this model, aminochrome selec-tively destroys individual neurons without spreading to neighbor-ing cells. Aminochrome is produced during neuromelanin synthe-sis, 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 plays a crucial role in regulating antioxidant enzymes, including DT-diaphorase and glutathione transferase M2-2. Nota-bly, certain dietary bioactive compounds can activate the KEAP1/NRF2 pathway, enhancing the production of these protec-tive enzymes. For example, the omega-3 fatty acids eicosapentae-noic acid and docosahexaenoic acid, as well as astaxan-thin—found in cold-water fish like salmon—have been shown to boost enzyme expression. This raises an important question: Could dietary interventions help prevent idiopathic Parkinson’s disease?","PeriodicalId":521283,"journal":{"name":"Preprints.org","volume":"1 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.preprints.org/frontend/manuscript/cee9705577a46dc7e2be5e2c9d0b7403/download_pub","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Preprints.org","FirstCategoryId":"0","ListUrlMain":"https://doi.org/10.20944/preprints202509.0025.v1","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
The molecular mechanism behind the loss of neuro-melanin-containing dopaminergic neurons in the nigrostriatal sys-tem in idiopathic Parkinson’s disease remains unclear. However, research suggests that aminochrome, an endogenous neurotoxin, may trigger the degeneration of these neurons through a sin-gle-neuron degeneration model. In this model, aminochrome selec-tively destroys individual neurons without spreading to neighbor-ing cells. Aminochrome is produced during neuromelanin synthe-sis, 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 plays a crucial role in regulating antioxidant enzymes, including DT-diaphorase and glutathione transferase M2-2. Nota-bly, certain dietary bioactive compounds can activate the KEAP1/NRF2 pathway, enhancing the production of these protec-tive enzymes. For example, the omega-3 fatty acids eicosapentae-noic acid and docosahexaenoic acid, as well as astaxan-thin—found in cold-water fish like salmon—have been shown to boost enzyme expression. This raises an important question: Could dietary interventions help prevent idiopathic Parkinson’s disease?