The study provides fascinating insights into the role of ferroptosis in Mn-induced neurotoxicity, particularly the emphasis on markers like GPX4 depletion and mitochondrial dysfunction. However, I found some aspects challenging to follow:
i. In Tables 1-3, the experimental conditions are briefly summarized, but it’s unclear how the animal models and Mn doses relate to real-world exposure levels. Could the authors clarify how these findings translate to environmental or occupational scenarios?
ii. The high-dose Mn exposure results are intriguing, but I couldn’t fully grasp how they connect to typical human exposure levels. Could the authors provide more context about the relevance of these doses?
iii. Fig. 1 illustrates key pathways in ferroptosis but doesn’t clearly show the experimental evidence supporting each connection. Could the authors explain how these pathways were validated in relation to Mn exposure?