Iron-frataxin involved in the protective effect of quercetin against alcohol-induced liver mitochondrial dysfunction

Liu J, Chen H, Lin H, Peng S, Chen L, Cheng X, Yao P, Tang Y.; J Nutr Biochem. 2022 Dec 29:109258. doi: 10.1016/j.jnutbio.2022.109258. Epub ahead of print. PMID: 36587874. 

 Frataxin deficiency reduced the protective effects of quercetin on mitochondria disordered by ethanol.

Drosophila melanogaster frataxin: protein crystal and predicted solution structure with identification of the iron-binding regions

Rodrigues AV, Batelu S, Hinton TV, Rotondo J, Thompson L, Brunzelle JS, Stemmler TL.; Acta Crystallogr D Struct Biol. 2023 Jan 1;79(Pt 1):22-30. doi: 10.1107/S2059798322011639. Epub 2023 Jan 1. PMID: 36601804. 

 The goal of this report is to provide structural details of the Drosophila melanogaster frataxin ortholog (Dfh), using both X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, in order to provide the foundational insight needed to understand the structure-function correlation of the protein.

Histopathology of the cerebellar cortex in essential tremor and other neurodegenerative motor disorders: comparative analysis of 320 brains

Elan D. Louis, Regina T. Martuscello, John T. Gionco, Whitney G. Hartstone, Jessica B. Musacchio, Marisa Portenti, Morgan McCreary, Sheng-Han Kuo, Jean-Paul G. Vonsattel & Phyllis L. Faust; Acta Neuropathol (2023). doi:10.1007/s00401-022-02535-z 

We conducted comparative analyses in a postmortem series of 320 brains on the severity and patterning of cerebellar cortex degenerative changes in ET (n = 100), other neurodegenerative disorders of the cerebellum [spinocerebellar ataxias (SCAs, n = 47, including 13 SCA3 and 34 SCA1, 2, 6, 7, 8, 14); Friedreich’s ataxia (FA, n = 13); multiple system atrophy (MSA), n = 29], and other disorders that may involve the cerebellum [Parkinson’s disease (PD), n = 62; dystonia, n = 19] versus controls (n = 50).

Mitochondrial Calcium Homeostasis in the Pathology and Therapeutic Application in Friedreich's Ataxia

Hongting Zhao, Zhuoyuan Li, Yutong Liu, Meng Zhang & Kuanyu Li. Neurosci. Bull. (2022). doi:10.1007/s12264-022-01007-4

Gambling associated risk-taking decision in cerebellar ataxia

Ruo-Yah Lai Natasha A. Desai Christian J. Amlang Chi-Ying R. Lin Tiffany X. Chen Michael J. Minyetty Nadia Amokrane Sheng-Han Kuo;  Parkinsonism & Related Disorders, Volume 0, Issue 0, 105252,  doi:10.1016/j.parkreldis.2022.105252 

People with cerebellar ataxia (CA) can develop impulsive and compulsive behaviors that significantly affect their and their family's quality of life. To further assess the decision-making process associated with these behaviors, we used the Iowa Gambling Task (IGT) to study people with CA.

CA cases obtained significantly lower IGT total scores than controls (−5.30 ± 37.53 vs. 21.30 ± 37.37, p = 0.004). In addition, those with CA made riskier decisions throughout the task compared to controls. Although both CA and controls learned to make decisions with more favorable outcomes over the course of completing the IGT, CA participants never matched the controls' performance. IGT performance did not correlate with ataxia severity or depressive symptoms.

SHAREHOLDER ALERT: Pomerantz Law Firm Investigates Claims On Behalf of Investors of Design Therapeutics, Inc.

NEW YORK, Dec. 26, 2022 /PRNewswire/ -- Pomerantz LLP is investigating claims on behalf of investors of Design Therapeutics, Inc. ("Design" or the "Company") (NASDAQ: DSGN). 

On or around March 24, 2021, Design conducted its initial public offering ("IPO"), selling 12 million shares of stock priced at $20.00 per share. Then, on December 7, 2022, Design reported initial data from a Phase 1 trial of DT-216 in patients with Friedreich ataxia. Among other results, Design said 16 patients on DT-216 and eight on placebo reported at least one treatment-emergent adverse event. On this news, Design's stock price fell sharply during intraday trading on December 8, 2022.

The psychosocial situation of families caring for children with rare diseases during the COVID-19 pandemic: results of a cross-sectional online survey

Lydia Rihm, Mareike Dreier, Farhad Rezvani, Silke Wiegand-Grefe & Jörg Dirmaier; Orphanet J Rare Dis 17, 449 (2022). doi:10.1186/s13023-022-02595-0 

 This study indicates a high psychosocial burden on family caregivers of children with RDs during the early COVID-19 pandemic, characterized by high distress levels and wide-ranging everyday problems, unmet psychosocial information needs, and reduced caregiver-reported HRQoL in children with RDs. The findings highlight the ongoing need for target group-specific, low-threshold support services (e.g., websites) during and after the pandemic.

Social concepts and the cerebellum: behavioural and functional connectivity signatures in cerebellar ataxic patients

Lopes da Cunha Pamela, Fittipaldi Sol, González Campo Cecilia, Kauffman Marcelo, Rodríguez-Quiroga Sergio, Yacovino Darío Andrés, Ibáñez Agustín, Birba Agustina and García Adolfo M. 2023; Phil. Trans. R. Soc., B3782021036420210364, doi:10.1098/rstb.2021.0364 

We compared behavioural outcomes between groups and examined their association with cerebellar connectivity. CA patients showed deficits in social text comprehension and normal scores in the non-social text. Also, social text outcomes in controls selectively correlated with connectivity between the cerebellum and key regions subserving multi-modal semantics and social cognition, including the superior and medial temporal gyri, the temporal pole and the insula. Conversely, brain-behaviour associations involving the cerebellum were abolished in the patients. Thus, cerebellar structures and connections seem involved in processing social concepts evoked by naturalistic discourse. Such findings invite new theoretical and translational developments integrating social neuroscience with embodied semantics.

Protection of dystrophic muscle cells using Idebenone correlates with the interplay between calcium, oxidative stress and inflammation

Amanda Harduim Valduga, Daniela Sayuri Mizobuti, Fernanda dos Santos Rapucci Moraes, Rafael Dias Mâncio, Luis Henrique Rapucci Moraes, Túlio de Almeida Hermes, Aline Barbosa Macedo, Elaine Minatel; Int J Exp Path. 2022; 00: 1- 9. doi:10.1111/iep.12463 

The Idebenone treatment was able to reduce the levels of oxidative stress markers, such as H2O2 and 4-HNE, as well as decreasing intracellular calcium influx in the dystrophic muscle cells. Regarding Idebenone effects on the anti-oxidant defence system, an up-regulation of catalase levels, glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity was observed in the dystrophic muscle cells. In addition, the Idebenone treatment was also associated with reduction in inflammatory molecules, such as nuclear factor kappa-B (NF-κB) and tumour necrosis factor (TNF) in mdx muscle cells.

Astrocytic mitochondrial frataxin—A promising target for ischemic brain injury

Hazra, R, Novelli, EM, Hu, X.; CNS Neurosci Ther. 2022; 00: 1- 6. doi:10.1111/cns.14068 

In the ischemic brain, hypoxia leads to mitochondrial dysfunction, insufficient energy production, and astrocyte activation. Yet, most studies investigating mitochondrial dysfunction in cerebral ischemia have focused exclusively on neurons. This review will highlight the importance of the morphological, molecular, and functional heterogeneity of astrocytes in their role in brain injuries and explore how activated astrocytes exhibit calcium imbalance, reactive oxygen species overproduction, and apoptosis. In addition, special focus will be given to the role of the mitochondrial protein frataxin in activated astrocytes during ischemia and its putative role in the pharmacological management of cerebral ischemia.