Elucidating the pathobiology of Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS) with its expanded RNA structure formation and proteinopathy DOI Creative Commons
Krishna Singh, Sakshi Shukla, Uma Shankar

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 14, 2024

Numerous neurological disorders are linked to sequences rich in guanine repeats found introns, exons, and regulatory regions of genes. These have been observed form stable G-quadruplex (GQ) structures both vitro vitro. Cerebellar Ataxia with Neuropathy Vestibular Areflexia Syndrome (CANVAS), a slowly progressive neurodegenerative disorder, is associated the biallelic expansion (AAGGG)n pathogenic second intron RFC1 gene. Though these G-rich other diseases protein loss function, RNA gain and/or not much known about pathological mechanism CANVAS. Herein, we report formation GQ conformations CANVAS-associated i.e., r(AAGGG)n, where 'r' stands for RNA. GQs critical regulators leading foci binding sequestration. They also alter causative processes like retention, which leads us hypothesize toxic Proteinopathy Various biophysical biomolecular assays characterized interactions three aggregation-prone RNA-binding proteins (RBPs): heterogeneous nuclear ribonucleoprotein H1/F (hnRNP H1/F), DGCR8 different [(AAGGG)9] vitro, further affirming hypothesis. The observations supported by molecular dynamics analysis cell-based studies, putting step closer elucidating mechanism(s) CANVAS neuropathy, paving way development innovative therapeutic interventions.

Язык: Английский

An Updated Canvas of the RFC1-mediated CANVAS (Cerebellar Ataxia, Neuropathy and Vestibular Areflexia Syndrome) DOI
Sakshi Shukla,

Kanav Gupta,

Krishna Singh

и другие.

Molecular Neurobiology, Год журнала: 2024, Номер unknown

Опубликована: Июнь 19, 2024

Язык: Английский

Процитировано

2
Elucidating the pathobiology of Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS) with its expanded RNA structure formation and proteinopathy DOI Creative Commons
Krishna Singh, Sakshi Shukla, Uma Shankar

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 14, 2024

Numerous neurological disorders are linked to sequences rich in guanine repeats found introns, exons, and regulatory regions of genes. These have been observed form stable G-quadruplex (GQ) structures both vitro vitro. Cerebellar Ataxia with Neuropathy Vestibular Areflexia Syndrome (CANVAS), a slowly progressive neurodegenerative disorder, is associated the biallelic expansion (AAGGG)n pathogenic second intron RFC1 gene. Though these G-rich other diseases protein loss function, RNA gain and/or not much known about pathological mechanism CANVAS. Herein, we report formation GQ conformations CANVAS-associated i.e., r(AAGGG)n, where 'r' stands for RNA. GQs critical regulators leading foci binding sequestration. They also alter causative processes like retention, which leads us hypothesize toxic Proteinopathy Various biophysical biomolecular assays characterized interactions three aggregation-prone RNA-binding proteins (RBPs): heterogeneous nuclear ribonucleoprotein H1/F (hnRNP H1/F), DGCR8 different [(AAGGG)9] vitro, further affirming hypothesis. The observations supported by molecular dynamics analysis cell-based studies, putting step closer elucidating mechanism(s) CANVAS neuropathy, paving way development innovative therapeutic interventions.

Язык: Английский

Процитировано

1