Search engine for discovering works of Art, research articles, and books related to Art and Culture
Javascript must be enabled to continue!
Staufen1 links RNA stress granules and autophagy in a model of neurodegeneration
View through CrossRef
AbstractSpinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by expansion of polyglutamine tract in the ATXN2 protein. We identified Staufen1 (STAU1) as an interactor of ATXN2, and showed elevation in cells from SCA2 patients, amyotrophic lateral sclerosis (ALS) patients, and in SCA2 mouse models. We demonstrated recruitment of STAU1 to mutant ATXN2 aggregates in brain tissue from patients with SCA2 human brain and in an SCA2 mouse model, and association of STAU1 elevation with dysregulation of SCA2-related transcript abundances. Targeting STAU1 in vitro by RNAi restored PCP2 transcript levels and lowering mutant ATXN2 also normalized STAU1 levels. Reduction of Stau1 in vivo improved motor behavior in an SCA2 mouse model, normalized the levels of several SCA2-related proteins, and reduced aggregation of polyglutamine-expanded ATXN2. These findings suggest a function for STAU1 in aberrant RNA metabolism associated with ATXN2 mutation, suggesting STAU1 is a possible novel therapeutic target for SCA2.
Springer Science and Business Media LLC
Title: Staufen1 links RNA stress granules and autophagy in a model of neurodegeneration
Description:
AbstractSpinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by expansion of polyglutamine tract in the ATXN2 protein.
We identified Staufen1 (STAU1) as an interactor of ATXN2, and showed elevation in cells from SCA2 patients, amyotrophic lateral sclerosis (ALS) patients, and in SCA2 mouse models.
We demonstrated recruitment of STAU1 to mutant ATXN2 aggregates in brain tissue from patients with SCA2 human brain and in an SCA2 mouse model, and association of STAU1 elevation with dysregulation of SCA2-related transcript abundances.
Targeting STAU1 in vitro by RNAi restored PCP2 transcript levels and lowering mutant ATXN2 also normalized STAU1 levels.
Reduction of Stau1 in vivo improved motor behavior in an SCA2 mouse model, normalized the levels of several SCA2-related proteins, and reduced aggregation of polyglutamine-expanded ATXN2.
These findings suggest a function for STAU1 in aberrant RNA metabolism associated with ATXN2 mutation, suggesting STAU1 is a possible novel therapeutic target for SCA2.
Related Results
ULK1 and ULK2 modulate different aspects of skeletal muscle autophagy
ULK1 and ULK2 modulate different aspects of skeletal muscle autophagy
<p>Macroautophagy, hereafter referred to as autophagy, is a catabolic process involving the degradation of cellular proteins and structures sequestered into a vesicle known a...
Detecting RNA–RNA interactome
Detecting RNA–RNA interactome
AbstractThe last decade has seen a robust increase in various types of novel RNA molecules and their complexity in gene regulation. RNA molecules play a critical role in cellular e...
Identification of stress specific autophagy regulators from tandem CRISPR screens
Identification of stress specific autophagy regulators from tandem CRISPR screens
Abstract
Autophagy is a conserved degradative process that promotes cellular homeostasis under stress conditions. Under nutrient starvation autophagy is largely non...
Modulation of RNA condensation by the DEAD-box protein eIF4A
Modulation of RNA condensation by the DEAD-box protein eIF4A
SUMMARY
Stress granules are condensates of non-translating mRNAs and proteins involved in the stress response and neurodegenerative diseases. Str...
Comparative Analysis of Functional Properties, Nutrient Composition and Sensory Quality of Bio-fortified and Traditionally Prepared Cassava Granules
Comparative Analysis of Functional Properties, Nutrient Composition and Sensory Quality of Bio-fortified and Traditionally Prepared Cassava Granules
The success of bio-fortification of cassava for production of vitamin A rich cassava granules commonly known as garri depends on the consumers’ acceptance. The study aimed at deter...
Effect of RNA preservation methods on RNA quantity and quality of field collected avian whole blood
Effect of RNA preservation methods on RNA quantity and quality of field collected avian whole blood
ABSTRACT
A limitation of comparative transcriptomic studies of wild avian populations continues to be sample acquisition and preservation to achi...
Abstract 1688: Autophagy inhibition enhances the antitumor effects of combretastatin A4 phosphate (CA4P).
Abstract 1688: Autophagy inhibition enhances the antitumor effects of combretastatin A4 phosphate (CA4P).
Abstract
Vascular disruptive agents such as CA4P cause an acute shutdown of the tumor vasculature resulting in metabolic stress and central tumor necrosis. However, ...