Neuropathology of Friedreich ataxia and its links to metabolic pathways

Mercado-Ayón E, Lazaropoulos MP, Mercado-Ayón Y, Lynch DR. Neuropathology of Friedreich ataxia and its links to metabolic pathways. Neurodegener Dis Manag. 2025 Dec 25:1-12. doi: 10.1080/17582024.2025.2607957. Epub ahead of print. PMID: 41447358. 

This review highlights recent insights into the neuropathology of FRDA, emphasizing the detailed developmental timing of neuroanatomical changes. It also focuses on selective mitochondrial metabolic pathways, including fatty acid metabolism, ceramide synthesis, and ketogenesis, which may underlie neuron-specific vulnerability and serve as potential targets for pharmacological or dietary intervention. The possibility of non-traditional interventions based on metabolic features of FRDA offers hope for ameliorating the severity of FRDA.

Neuropathology of Friedreich ataxia and its links to metabolic pathways