Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders

Raka RN, Zhang Z, Xiao J, Wu H. Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders. Comput Biol Med. 2026 May 15;208:111681. doi: 10.1016/j.compbiomed.2026.111681. Epub 2026 Apr 14. PMID: 41985299.  

The article explores the relationship with Friedreich's Ataxia through integrative network pharmacology. Friedreich's Ataxia is analyzed as one of the key neurodegenerative disorders sharing molecular pathways like oxidative stress and neuroinflammation. 

The study identifies specific compounds in essential oils that target proteins linked to the disease, suggesting a multi-target computational framework for potential neuroprotective treatments. It focuses on how these compounds interact with GPCR and non-GPCR targets to potentially modulate the biological dysfunctions seen in ataxia patients.

Listening in Spatialized Noise-Sentences (LiSN-S) as a Measure of Auditory Function in Friedreich Ataxia

Ali SAH, Early J, Farmer JM, Gelbard S, Corben L, Rance G, Lynch DR. Listening in Spatialized Noise-Sentences (LiSN-S) as a Measure of Auditory Function in Friedreich Ataxia. Cerebellum. 2026 Apr 24;25(3):60. doi: 10.1007/s12311-026-02000-7. PMID: 42029806; PMCID: PMC13109125. 

 LiSN -S testing captures audiologic dysfunction in FRDA in a manner that appears to dependent on genetic severity and to a lesser degree time.

Hypomagnetic Field Exposure Alters Iron-Sulfur Homeostasis and Oxidative Balance in a Frataxin-Deficient Insect System

Kang HM, Li B, Yan S, Zhang LL, Wan GJ, Zhang JZ, Pan WD. Hypomagnetic Field Exposure Alters Iron-Sulfur Homeostasis and Oxidative Balance in a Frataxin-Deficient Insect System. Insects. 2026 Apr 1;17(4):373. doi: 10.3390/insects17040373. PMID: 42042415; PMCID: PMC13116274. 

 HMF elevated reactive oxygen species (ROS) in frataxin-deficient brains. Transcriptomic analysis identified 202 differentially expressed genes under HMF in frataxin-silenced flies, including key regulators of iron metabolism and oxidative stress pathways. These findings demonstrate that HMF disrupts tissue-specific iron and sulfur homeostasis and intensifies oxidative stress in a frataxin-deficient insect system, underscoring its role as an environmental factor capable of aggravating metabolic fragility.

Astrocytic frataxin deficiency drives neurocognitive impairment in sickle cell mice

Novelli EM, Lenhart SC, Foley LM, Sekar N, Mondal P, Wang H, Hitchens TK, Ghosh S, Chan SY, Hu X, Hazra R. Astrocytic frataxin deficiency drives neurocognitive impairment in sickle cell mice. PNAS Nexus. 2026 Apr 8;5(4):pgag106. doi: 10.1093/pnasnexus/pgag106. PMID: 42037666; PMCID: PMC13108596. 

 Herein, we report that sickle cell mice (SS) have reduced expression of frataxin (FXN), a mitochondrial protein, in their astrocytes compared with normal control (AA) mice. A newly generated sickle bone marrow chimeric mouse with astrocyte-specific deletion of FXN (SSFXN-KO) showed worsening white-matter neuroaxonal damage compared with the normal mice lacking astrocytic FXN (AAFXN-KO) as well as with the SS mice with wild-type FXN expression (SSFXN-WT). The SSFXN-KO mice exhibited impaired cognitive function assessed by the functional novel object recognition (NOR) tests. Induction of FXN improved cognitive responses in the SS mice. Overall, our data demonstrate that astrocytic FXN plays a pivotal role in regulating neuroaxonal health and cognitive function in SCD.

BRD4 recruitment desilences transcription without erasure or depletion of repressive chromatin

BRD4 recruitment desilences transcription without erasure or depletion of repressive chromatin. Christopher J. Brandon, Sarah Robinson-Thiewes, Mangesh Kaulage, Wojciech Rosikiewicz, Matthew J. Cuneo, Joseph Brett, Jindpreet Kandola, Walter H. Lang, Jonathan Low, Ashraf Mohammed, Adithi Danda, Sam Rider, Marcus Valentine, Jason Ochoada, Brandon Young, Theresa Nguyen, Sandra J. Kietlinska, Aaron B. Taylor, Burkhard Hoeckendorf, Patrick Rodrigues, Wenwei Lin, Khaled Khairy, Beisi Xu, Anang A. Shelat, Taosheng Chen, Tanja Mittag, Aseem Z. Ansari bioRxiv 2026.04.10.717856; doi:10.64898/2026.04.10.717856

We find that BRD4 readily partitions into phase separated HP1 condensates in vitro and into HP1 puncta in patient-derived cells, thus presenting a mechanistic explanation for desilencing transcription without the dispersal of mesoscale repressive chromatin. Epigenetic drugs that gate sequential steps in transcription, synergistically stimulate FXN expression while concomitantly increasing, rather than eliminating, repressive H3K9me3 and HP1 levels. More broadly, this study highlights the dynamic nature of repressive chromatin and the context-dependence of epigenetic marks in regulating gene expression.

Modeling Friedreich’s ataxia with Bergmann glia-enriched human cerebellar organoids

Ryu, S., Inman, J., Hong, H. et al. Modeling Friedreich’s ataxia with Bergmann glia-enriched human cerebellar organoids. Commun Biol (2026). doi:10.1038/s42003-026-10180-5 

Furthermore, by generating hCBOs from patients with Friedreich’s ataxia (FRDA), we reveal disease-specific phenotypes that can be reversed by histone deacetylase (HDAC) inhibitors and gene editing by CRISPR-Cas9. Taken together, our advanced hCBO model provides new opportunities to investigate the mechanisms of cerebellar ontogenesis and utilize patient-derived iPSCs for translational research.

Glial-specific mitochondrial failure and redox imbalance drive regional vulnerability in Friedreich ataxia

Glial-specific mitochondrial failure and redox imbalance drive regional vulnerability in Friedreich ataxia. Arabela Sanz-Alcazar, Marta Portillo-Carrasquer, Israel Manjarres-Raza, Maria Pazos-Gil, Fabien Delaspre, Jordi Tamarit, Juan P. Bolanos, Joaquim Ros, Elisa Cabiscol; bioRxiv 2026.05.01.722124; doi:10.64898/2026.05.01.722124 

 These results highlight the vulnerability of sensory neurons and their supporting satellite glial cells. In contrast, in the cerebrum and cerebellum, astrocytes displayed earlier and more severe alterations than neurons, including impaired respiratory chain efficiency, disrupted complex I-III supercomplex interaction, elevated ROS, and hallmarks of ferroptosis. Neuronal abnormalities emerged later, suggesting that glial dysfunction precedes -or drives- neuronal pathology within the central nervous system. Overall, these findings reveal pronounced region and cell-type-specific vulnerabilities in FA and support the importance of targeting glial mechanisms -particularly iron dysregulation, oxidative stress, and ferroptosis- as targets for potential therapeutic strategies.