Investigation of the effects of β-hydroxybutyrate on ferroptosis mechanisms in a neurotoxicity model: A new perspective on ketogenic diet approach in neurodegenerative diseases
Project no. 32186 · Status: Kapanmış (Yayın bekleniyor) · 2024
Summary
<p>Ferroptosis is an iron-dependent cell death mechanism that has been identified in the last decade. Accumulated Fe+2 oxidizes lipids. The reduction and metabolism of lipid peroxides is insufficient and lipid peroxides accumulate and join the cell membrane, leading to oxidative cell death. In Parkinson's disease, which is characterized by degeneration of neurons in the substantia nigra pars compacta region with high iron content, the neuroprotective effect of iron chelators suggests that it may be related to ferroptosis pathways.</p><p>Ketogenic diet, which is known to improve cognitive and motor functions in many neurological diseases, increases the amount of ketone bodies in the blood, most notably β-hydroxybutyrate (BHB). It has been shown in the literature that BHB reduces reactive oxygen species and has neuroprotective effects. Although it is thought that its antioxidant properties cause these positive effects, the fact that the same results cannot be obtained with antioxidant substances alone suggests that other mechanisms are effective.</p><p>In the literature, it is seen that ferroptosis and BHB have effects on GSH and antioxidant mechanisms, and that their paths intersect in many mechanisms such as apoptosis and inflammation, but the effects of BHB have not yet been evaluated in terms of ferroptosis. In our study, BHB doses at normal, ketogenic and ketoacidosis levels that exemplify different metabolic conditions in neurotoxic cell cultures will be investigated and ferroptosis mechanisms will be investigated.</p><p>In neurotoxicity, the effects of BHB and other ferroptosis activators and inhibitors on membrane damage, iron accumulation, lipid peroxidation and reactive oxygen species in cells will be evaluated. In addition, it is planned to demonstrate ferroptosis microscopically with the 3F3-FMA antibody, which has been determined to be specific to ferroptosis, using the immunofluorescence method.</p><p>Our aim is to contribute to the elucidation of the mechanisms underlying neurodegenerative diseases such as Parkinson's Disease by drawing attention to the relationship between BHB and ferroptosis, and to shed light on molecular mechanisms in terms of directing patients and healthy individuals to proper nutrition programs. The results we will obtain will also provide a new perspective for future research.</p>