Unraveling the Role of Ataxin-2 in Metabolism

Ataxin-2 is a polyglutamine protein with an important role in RNA metabolism and translation regulation. Emerging data suggest that ataxin-2 might impact on metabolic status and body weight. Several genetic linkage studies have implicated the ATXN2 locus and adjacent regions (12q23–24) in the risk of obesity, hypertension, and cardiovascular disease. Ataxin-2 knockout or depletion in different animal models leads to hyperphagia, obesity, altered lipid metabolism, and insulin resistance. Starvation and mTOR inhibition induce ataxin-2 expression, and ataxin-2 in turn regulates the PI3K/mTOR pathway. Ataxin-2 is present in the hypothalamus, the brain region responsible for control energy and body homeostasis. It could therefore affect physiological functions such as body weight and food intake, circadian rhythm, stress response, and longevity. Ataxin-2 is a polyglutamine protein implicated in several biological processes such as RNA metabolism and cytoskeleton reorganization. Ataxin-2 is highly expressed in various tissues including the hypothalamus, a brain region that controls food intake and energy balance. Ataxin-2 expression is influenced by nutritional status. Emerging studies discussed here now show that ataxin-2 deficiency correlates with insulin resistance and dyslipidemia, an action mediated via the mTOR pathway, suggesting that ataxin-2 might play key roles in metabolic homeostasis including body weight regulation, insulin sensitivity, and cellular stress responses. In this review we also discuss the relevance of ataxin-2 in the hypothalamic regulation of energy balance, and its potential as a therapeutic target in metabolic disorders such as obesity. Ataxin-2 is a polyglutamine protein implicated in several biological processes such as RNA metabolism and cytoskeleton reorganization. Ataxin-2 is highly expressed in various tissues including the hypothalamus, a brain region that controls food intake and energy balance. Ataxin-2 expression is influenced by nutritional status. Emerging studies discussed here now show that ataxin-2 deficiency correlates with insulin resistance and dyslipidemia, an action mediated via the mTOR pathway, suggesting that ataxin-2 might play key roles in metabolic homeostasis including body weight regulation, insulin sensitivity, and cellular stress responses. In this review we also discuss the relevance of ataxin-2 in the hypothalamic regulation of energy balance, and its potential as a therapeutic target in metabolic disorders such as obesity. transgenic model of mice expressing a mutated mouse Atxn2 gene with 42 CAG repeats on a C57BL/6 background. transgenic model of mice expressing a mutated human ATXN2 gene with 72CAG repeats. This mouse model was produced using a bacterial artificial chromosome (BAC) on an FVB background. the physical process at the end of cell cycle which divides the cytoplasm of a parental cell into two daughter cells. The process of cytokinesis is dynamic and requires the assembly of several proteins including actin filaments. also called mRNP granules, these form upon cellular stress. They are dynamic structures formed from mRNAs, translation initiation factors, and several RNA-binding proteins. Stress granule formation conserves cellular energy by limiting the translation of unnecessary mRNAs, thereby producing only essential proteins for survival. Once the stress is surpassed, stress granules disassemble. the deposition of lipid-containing foam cells, generally in association with hyperlipidemia. Xanthomas are localized mainly in joints and tendons.