Low expression of Frataxin might contribute to diabetic peripheral neuropathy in a mouse model
Year: 2024
Type: article
Abstract: Diabetes is one of the most prevalent metabolic disorders, and its incidence has been experiencing a steady annual rise in recent years. Diabetic peripheral neuropathy (DPN) represents the most frequent adverse complication, exerting a profound impact on the quality of life for those suffering from diabetes. The etiology of DPN is complex, including impaired mitochondrial function. Iron-sulfur clusters (Fe–S) are essential cofactors for numerous essential enzymes crucial for mitochondrial function. Our previous study showed that expression of Frataxin, encoded by the Fxn gene, is downregulated in leptin receptor knockout (so-called db/db) mice, a commonly used DPN mouse model. Fxn is one of the core components of Fe–S biogenesis machinery. Here, we found that the mitochondria-targeted antioxidant SS-31 markedly improved the behavioral indices and significantly mitigated the damage to the sciatic nerve. SS-31 treatment effectively elevated Fxn expression, meliorated mitochondrial function, and inflammation in the sciatic nerve (SCN). We also found that SS-31 effectively mitigated high glucose-induced disruption of iron and redox homeostasis in RSC96 cells, a typical cell model of DPN, thereby improving mitochondrial function. These findings suggest enhancing Fe–S biogenesis could be an effective therapeutic strategy for treating DPN. • SS-31, a mitochondria-targeted antioxidant, improves behavior, mitigates sciatic nerve damage in db/db mice with DPN. • SS-31 treatment enhances Fxn expression, mitochondrial function, and reduces inflammation in SCN. • In vitro experiments with RSC96 cells show that SS-31 effectively mitigated high glucose-induced disruption of iron and redox homeostasis.
Authors: Siyu Xia, Lin Wu, Jing Chen, Kuanyu Li, Dezhi Bian
Institution: Nanjing University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,880
OpenAlex ID: W4405633075