Harshly Oxidized Activated Charcoal Enhances Protein Persulfidation with Implications for Neurodegeneration as Exemplified by Friedreich’s Ataxia DOI Creative Commons
Anh Tran Tram Vo, Uzair Khan, Anton V. Liopo

et al.

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(24), P. 2007 - 2007

Published: Dec. 13, 2024

Harsh acid oxidation of activated charcoal transforms an insoluble carbon-rich source into water-soluble, disc structures graphene decorated with multiple oxygen-containing functionalities. We term these pleiotropic nano-enzymes as “pleozymes”. A broad redox potential spans many crucial reactions including the hydrogen sulfide (H2S) to polysulfides and thiosulfate, dismutation superoxide radical (O2−*), NADH NAD+. The H2S is predicted enhance protein persulfidation—the attachment sulfur cysteine residues. Persulfidated proteins act intermediates, persulfidation protects from irreversible ubiquitination, providing important means signaling. Protein believed decline in several neurological disorders aging. Importantly, consistent role signaling, master antioxidant transcription factor Nrf2 regulated by Keap1’s persulfidation. Here, we demonstrate that pleozymes increased overall cells apparently healthy individuals mitochondrial mutation responsible for Friedreich’s ataxia. further find specifically enhanced Keap1 persulfidation, subsequent accumulation Nrf2’s targets.

Language: Английский

Polyglutamine Ataxias in Denmark: Incidence and Relative Frequencies of SCA1, 2, 3, 6, 7, 17 and DRPLA in a Nationwide Cohort DOI Creative Commons

Rosa Dam Waerling,

Jenny Blechingberg,

Jesper Kayser

et al.

The Cerebellum, Journal Year: 2025, Volume and Issue: 24(3)

Published: March 14, 2025

Abstract Polyglutamine ataxias are autosomal dominantly inherited neurodegenerative disorders in which the molecular aetiology is an expanded CAG glutamine-encoding repeat causative genes. At present, there no effective treatment, but several ongoing trials addressing polyglutamine increasing need of knowledge about prevalence and relative frequencies different subtypes. To identify all individuals with genetically confirmed ataxia Denmark, determine frequency subtypes estimate incidences. Retrospective data on clinical tests performed Denmark during last 15 years. 215 alleles full penetrant pathogenic range genes were identified. The most frequent was SCA6 accounts for 42% identified individuals, followed by SCA2 SCA3 both account approximately 20% each. Incidence rates calculated. study reveals subtype distribution incidence priming Danish cohort future as developments treatment advances.

Language: Английский

Citations

0
Harshly Oxidized Activated Charcoal Enhances Protein Persulfidation with Implications for Neurodegeneration as Exemplified by Friedreich’s Ataxia DOI Creative Commons
Anh Tran Tram Vo, Uzair Khan, Anton V. Liopo

et al.

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(24), P. 2007 - 2007

Published: Dec. 13, 2024

Harsh acid oxidation of activated charcoal transforms an insoluble carbon-rich source into water-soluble, disc structures graphene decorated with multiple oxygen-containing functionalities. We term these pleiotropic nano-enzymes as “pleozymes”. A broad redox potential spans many crucial reactions including the hydrogen sulfide (H2S) to polysulfides and thiosulfate, dismutation superoxide radical (O2−*), NADH NAD+. The H2S is predicted enhance protein persulfidation—the attachment sulfur cysteine residues. Persulfidated proteins act intermediates, persulfidation protects from irreversible ubiquitination, providing important means signaling. Protein believed decline in several neurological disorders aging. Importantly, consistent role signaling, master antioxidant transcription factor Nrf2 regulated by Keap1’s persulfidation. Here, we demonstrate that pleozymes increased overall cells apparently healthy individuals mitochondrial mutation responsible for Friedreich’s ataxia. further find specifically enhanced Keap1 persulfidation, subsequent accumulation Nrf2’s targets.

Language: Английский

Citations

0