SIRT2 Ablation Has No Effect on Tubulin Acetylation in Brain, Cholesterol Biosynthesis or the Progression of Huntington's Disease Phenotypes In Vivo

Huntington's disease (HD) is a devastating neurodegenerative disorder for which there are no disease-modifying treatments. The molecular pathogenesis of HD is complex and many mechanisms and cellular processes have been proposed as potential sites of therapeutic intervention. However, prior to embarking on drug development initiatives, it is essential that therapeutic targets can be validated in mammalian models of HD. Previous studies in invertebrate and cell culture HD models have suggested that inhibition of SIRT2 could have beneficial consequences on disease progression. SIRT2 is a NAD[superscript +]-dependent deacetylase that has been proposed to deacetylate α-tubulin, histone H4 K16 and to regulate cholesterol biogenesis – a pathway which is dysregulated in HD patients and HD mouse models. We have utilized mice in which SIRT2 has been reduced or ablated to further explore the function of SIRT2 and to assess whether SIRT2 loss has a beneficial impact on disease progression in the R6/2 mouse model of HD. Surprisingly we found that reduction or loss of SIRT2 had no effect on the acetylation of α-tubulin or H4K16 or on cholesterol biosynthesis in the brains of wild type mice. Equally, genetic reduction or ablation of SIRT2 had no effect on HD progression as assessed by a battery of physiological and behavioural tests. Furthermore, we observed no change in aggregate load or levels of soluble mutant huntingtin transprotein. Intriguingly, neither the constitutive genetic loss nor acute pharmacological inhibition of SIRT2 affected the expression of cholesterol biosynthesis enzymes in the context of HD. Therefore, we conclude that SIRT2 inhibition does not modify disease progression in the R6/2 mouse model of HD and SIRT2 inhibition should not be prioritised as a therapeutic option for HD.American Parkinson Disease Association, Inc. (Fellowship)Johnson & Johnson. Pharmaceutical Research & Development (Fellowship

Adaptation Study of the Mindful Eating Questiionnare (MEQ) into Turkish

Adaptation Study of the Mindful Eating Questionnare (MEQ) into Turkish Objective: In this study we aimed to define the mindful eating and discover the reliability and validity analyses of Mindful Eating Questionnare (MEQ) in Turkish sample, which has been developed to evaluate the relationship between eating behavior and mindful eating. Method: 360 volunteer university students included to our study. Participants in the survey asked to fill Turkish form of MEQ and Eating Attitude Test (EAT) completely. The study was completed with 318 participants fully filled the scales. Results: For reliability and validity of Turkish version of MEQ; internal consistency (cronbach alfa 0.733), item-total score analyses, factor analyses, parallel form correlations (As MEQ scores increase and both EAT scores and EAT score group (cutoff:30) increases) and factor correlations [As MEQ scores increase, Disinhibition (r=0.739), Emotional Eating (r=0.700), Control of Eating (r=0.594), Eating Discipline (r=0.449), Mindfullness (r=0.523), Enterferance (r=0.502) increasings are statistically significant (p [JCBPR 2016; 5(3.000): 125-134

Correction: SIRT2 Ablation Has No Effect on Tubulin Acetylation in Brain, Cholesterol Biosynthesis or the Progression of Huntington's Disease Phenotypes In Vivo.

[This corrects the article DOI: 10.1371/journal.pone.0034805.]

SIRT1 Suppresses β-Amyloid Production by Activating the α-Secretase Gene ADAM10

A hallmark of Alzheimer's disease (AD) is the accumulation of plaques of Aβ 1–40 and 1–42 peptides, which result from the sequential cleavage of APP by the β and γ-secretases. The production of Aβ peptides is avoided by alternate cleavage of APP by the α and γ-secretases. Here we show that production of β-amyloid and plaques in a mouse model of AD are reduced by overexpressing the NAD-dependent deacetylase SIRT1 in brain, and are increased by knocking out SIRT1 in brain. SIRT1 directly activates the transcription of the gene encoding the α-secretase, ADAM10. SIRT1 deacetylates and coactivates the retinoic acid receptor β, a known regulator of ADAM10 transcription. ADAM10 activation by SIRT1 also induces the Notch pathway, which is known to repair neuronal damage in the brain. Our findings indicate SIRT1 activation is a viable strategy to combat AD and perhaps other neurodegenerative diseases.American Parkinson Disease Association, Inc. (Postdoctoral Fellowship)National Institutes of Health (U.S.)Paul F. Glenn Foundatio

Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction

Mammalian life span can be extended by both calorie restriction (CR) and mutations that diminish somatotropic signaling. Sirt1 is a mediator of many effects of CR in mammals, but any role in controlling somatotropic signaling has not been shown. Since the somatotropic axis is controlled by the brain, we created mice lacking Sirt1 specifically in the brain and examined the impacts of this manipulation on somatotropic signaling and the CR response. These mutant mice displayed defects in somatotropic signaling when fed ad libitum, and defects in the endocrine and behavioral responses to CR. We conclude that Sirt1 in the brain is a link between somatotropic signaling and CR in mammals