The role of frataxin (FXN) has been studied extensively in Friedreich ataxia patients, however, the molecular bases underlining the sex steroid-dependent gene expression profiles of FXN in adult tissues are unknown. The author describes the molecular characterization of hamster FXN by examining the sexually dimorphic expression and its regulation by sex steroids. Sequence analysis of FXN cDNA showed 630 bp-long ORF encoding 209 amino acids. qPCR analysis revealed that FXN is detected in a wide range of tissues, with the highest expression in the heart, liver, and epididymis, and the weakest expression in the lung, spleen, uterus, and gut. In the male Harderian gland (HG), castration decreased FXN expression, while dihydrotestosterone (DHT) administration reestablished levels. FXN expression levels were higher in the male HG than the female HG. Expression levels in endocrine tissues showed a certain degree of sexual dimorphism; the transcript in the testis was significantly higher than those in the ovary. The effects of the estrous cycle on FXN expression remained unchanged in the HG, ovary, and adrenal glands; however, in the pancreas, the FXN mRNA was overexpressed during proestrus and exhibited sexual dimorphism as compared to the male pancreas. The mRNA expression results indicated that Harderian FXN may play a dynamic role in intracellular Fe of heme required for processing cytochromes and other hemeproteins, also suggesting that the moderate sexual dimorphism present in the HG and gonads could be regulated by androgens, while sexually dimorphic expression of FXN in the female pancreas may be controlled by sex steroids.

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Autosomal recessive cerebellar ataxias (ARCA) are a group of rare and heterogynous neurodegenerative diseases mainly characterized by unbalance and walking difficulty and movement incoordination. The aim of this study is to clinically and paraclinically characterize ARCA in the department of Neurology at the Teaching Hospital of Point G and identify the underlying genetic defect. The authors have conducted a longitudinal and prospective study from January 2018 to December 2020. Patients with ARCA phenotype seen in the Department of Neurology at the Teaching Hospital of Point "G" were enrolled. 7 families totaling 13 patients were enrolled after giving an informed verbal and written consent. The sex ratio was 2.2 in favor of males, Kayes region and Fulani ethnic group were respectively the most represented region and ethnic group. Walking difficulty represented the major symptom followed by loss of vibration and joint sense, nystagmus, dysarthria and skeletal deformities. Alpha-foetoprotein level was high in one patient. Genetic testing confirmed Friedreich ataxia in one family and was not conclusive in 4 families. This study showed that ARCA are not uncommon in Mali and genetic testing is crucial to confirm the diagnosis.

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Ferroptosis is a type of regulated cell death characterized by intracellular accumulation of iron and reactive oxygen species, inhibition of system Xc-, glutathione depletion, nicotinamide adenine dinucleotide phosphate oxidation and lipid peroxidation. Since its discovery and characterization in 2012, many efforts have been made to reveal the underlying mechanisms, modulating compounds, and its involvement in disease pathways. Ferroptosis inducers include erastin, sorafenib, sulfasalazine and glutamate, which, by inhibiting system Xc-, prevent the import of cysteine into the cells. RSL3, statins, Ml162 and Ml210 induce ferroptosis by inhibiting glutathione peroxidase 4 (GPX4), which is responsible for preventing the formation of lipid peroxides, and FIN56 and withaferin trigger GPX4 degradation. On the other side, ferroptosis inhibitors include ferrostatin-1, liproxstatin-1, α-tocopherol, zileuton, FSP1, CoQ10 and BH4, which interrupt the lipid peroxidation cascade. Additionally, deferoxamine, deferiprone and N-acetylcysteine, by targeting other cellular pathways, have also been classified as ferroptosis inhibitors. Increased evidence has established the involvement of ferroptosis in distinct brain diseases, including Alzheimer's, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, multiple sclerosis, and Friedreich's ataxia. Thus, a deep understanding of how ferroptosis contributes to these diseases, and how it can be modulated, can open a new window of opportunities for novel therapeutic strategies and targets. Other studies have shown a sensitivity of cancer cells with mutated RAS to ferroptosis induction and that chemotherapeutic agents and ferroptosis inducers synergize in tumor treatment. Thus, it is tempting to consider that ferroptosis may arise as a target mechanistic pathway for the treatment of brain tumors. Therefore, this work provides an up-to-date review on the molecular and cellular mechanisms of ferroptosis and their involvement in brain diseases. In addition, information on the main ferroptosis inducers and inhibitors and their molecular targets is also provided.

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This month's Research Update covers the following topics:

• First Medication to Treat Friedreich's Ataxia Approved by FDA
• The FARA Fellow Program
• Recent FARA Funded FA Publications
• Recent FA Publications
• FARA Forum Webinars
• Grant Opportunities
• Meetings of Interest to the FA Community
• Job Advertisements

Read the full Monthly Research Update