Molecular imaging of NAD<sup>+</sup>‐dependent deacetylase SIRT1 in the brain

Xu, Yulong; Chen, Zude; Wey, Hsiao‐Ying; Liang, Yingxia; Tanzi, Rudolph E.; Zhang, Can; Wang, Changning

doi:10.1002/alz.12344

Cited by 4 publications

(4 citation statements)

References 37 publications

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“…SIRT5 combined with the inhibitory effects of SIRT2 senhanced the innate in ammatory responses in macrophages by promoting acetylation of p65 and activation of NF-kB pathway21-23. Kane [22] in 2018 and Xu [23] in 2021 reviewed respectively that sirt1 was located in both nucleus and cytoplasm whereas sirt2 only detected in cytoplasm. In male mice, reduced eNAMPT levels and impaired NAD+ /SIRT1 pathway in the nucleus accumbens (NAc), a brain region known to encode the rewarding properties of social behavior, is accociated with peripubertal stress-induced increase in adiposity.…”

Section: Discussionmentioning

confidence: 99%

Exercise coupled with calorie restriction reduces SIRT1 and SIRT2 in female obese adolescents

Liu,

He,

Mao

et al. 2023

Preprint

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Background: As exercise coupled with calorie restriction was a most effective method for long-term weight control, whether exercise coupled with calorie restriction controls the expression of SIRT1 and SIRT2 and how the mechanisms work become important. Long-term benefits of conservative treatments in obese adolescents are limited, except for exercise training. Exercise training coupled with calorie restriction as a most effective method for long-term weight control has become increasingly considerable. Methods: Statistical significance for serum biomarkers associated with fat etabolism and longevity measured before and after intervention was evaluated using a paired sample t-test. Correlation coefficients were used to examine the relationships between fat metabolism and longevity biomarkers and physical composition parameters. Results: Physical composition parameters revealed a significant decline after 4-week intervention involving in exercise training coupled with calorie restriction(p < 0.05). Exercise coupled with dietary restriction decreases circulating serum SIRT1 and SIRT2 levels(p< 0.05). Circulating serum SIRT2 levels negatively correlate with vital capacity before 4-week intervention(p < 0.05). Circulating serum IGF1/IGFBP3 levels positively correlate with vital capacity after 4-week intervention(p < 0.05). Conclusions: 4-week exercise training and calorie restriction may upregulate Sirt1 gene expression in nucleus and downregulate mRNA translation in cytoplasm,which in turn, reduced circulating Sirt1 and Sirt2.

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Section: Discussionmentioning

confidence: 99%

Exercise coupled with calorie restriction reduces SIRT1 and SIRT2 in female obese adolescents

Liu,

He,

Mao

et al. 2023

Preprint

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“…11 Positron emission tomography (PET) is a noninvasive molecular imaging modality that offers the quantification and visualization of intricate biochemical processes. 12 PET imaging, utilizing radiotracers such as [ 18 F]-2-fluorobenzoylaminohexanoicanilide 13 and [ 11 C]WL-1, 14 enables noninvasive monitoring of SIRT1 expression activity. These radiotracers, specific to SIRT1, facilitate the visualization of its spatial and temporal dynamics in living organisms.…”

Section: Introductionmentioning

confidence: 99%

Development and Characterization of a Novel Carbon-11 Labeled Positron Emission Tomography Radiotracer for Neuroimaging of Sirtuin 1 with Benzoxazine-Based Compounds

Wang,

Liu,

Wang

et al. 2024

DDDT

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Introduction Sirtuins (SIRTs) comprise a group of histone deacetylase enzymes crucial for regulating metabolic pathways and contributing significantly to various disease mechanisms. Sirtuin 1 (SIRT1), among the seven known mammalian homologs, is extensively investigated and understood, playing a key role in neurodegenerative disorders and cancer. This study focuses on potential as a therapeutic target for conditions such as Parkinson’s disease (PD), Huntington’s disease (HD), and Alzheimer’s disease (AD). Methods Utilizing positron emission tomography (PET) as a noninvasive molecular imaging modality, we aimed to expedite the validation of a promising sirtuin 1 inhibitor for clinical trials. However, the absence of a validated sirtuin 1 PET radiotracer impedes clinical translation. We present the development of [ 11 C] 1 , and 11 C-labeled benzoxazine-based derivative, as a lead imaging probe. The radiosynthesis of [ 11 C] 1 resulted in a radiochemical yield of 31 ± 4%. Results Baseline studies demonstrated that [ 11 C] 1 exhibited excellent blood-brain barrier (BBB) penetration capability, with uniform accumulation throughout various brain regions. Self-blocking studies revealed that introducing an unlabeled compound 1 , effectively blocking sirtuin 1, led to a substantial reduction in whole-brain uptake, emphasizing the in vivo specificity of [ 11 C] 1 for sirtuin 1. Discussion The development of [ 11 C] 1 provides a valuable tool for noninvasive imaging investigations in rodent models with aberrant sirtuin 1 expression. This novel radiotracer holds promise for advancing our understanding of sirtuin 1’s role in disease mechanisms and may facilitate the validation of sirtuin 1 inhibitors in clinical trials.

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“…Our group has previously disclosed several novel radiotracers for PET imaging of epigenetic enzymes, 22−26 that can be used to visualize SIRT1 in the brain. 27 [ 11 C]WL-1 displays stable metabolism as well as proper kinetics and distribution. In the present study, we investigate the efficacy of [ 11 C]WL-1 for imaging SIRT1 in a mouse model of early-stage ALD.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Our group has previously disclosed several novel radiotracers for PET imaging of epigenetic enzymes, − among which [ 11 C]Martinostat has been successful in advancing the first-in-human trials for imaging class-I histone deacetylases (HDACs). More recently, we have developed and characterized a new radiotracer ([ 11 C]WL-1, also known as [ 11 C]8) that can be used to visualize SIRT1 in the brain . [ 11 C]WL-1 displays stable metabolism as well as proper kinetics and distribution.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Positron Emission Tomography Imaging of SIRT1 in a Model of Early-Stage Alcoholic Liver Disease

et al. 2023

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Accrued evidence has indicated that epigenetic mechanisms altered by alcohol have been implicated in the progression and development of alcoholic liver disease (ALD). SIRT1 plays an important role in ALD progression and has emerged as a promising therapeutic target for treating ALD. The purpose of this study is to investigate the efficacy of [ 11 C]WL-1 for quantitative imaging of SIRT1 in mouse models of early-stage ALD. Positron emission tomography/computerized tomography (PET/CT) imaging was carried out 60 min following the injection of [ 11 C]WL-1 in mouse models of early-stage ALD and normal control mice. The time−activity curves for ALD mouse livers showed remarkably decreased total uptake of [ 11 C]WL-1 relative to that for control mouse livers. Moreover, compared with the normal control mice, decreased uptake in the cortex, hippocampus, and cerebellum was also observed in early-stage ALD mice, while the uptake of [ 11 C]WL-1 in amygdala showed no significant changes. Western blot analysis confirmed that the protein levels of SIRT1 in the brains of early-stage ALD mice were decreased significantly when compared to the normal control mouse brains. Collectively, PET imaging with [ 11 C]WL-1 would facilitate future clinical studies, aiming to demonstrate the roles of SIRT1 in ALD.

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Molecular imaging of NAD⁺‐dependent deacetylase SIRT1 in the brain

Cited by 4 publications

References 37 publications

Exercise coupled with calorie restriction reduces SIRT1 and SIRT2 in female obese adolescents

Exercise coupled with calorie restriction reduces SIRT1 and SIRT2 in female obese adolescents

Development and Characterization of a Novel Carbon-11 Labeled Positron Emission Tomography Radiotracer for Neuroimaging of Sirtuin 1 with Benzoxazine-Based Compounds

Noninvasive Positron Emission Tomography Imaging of SIRT1 in a Model of Early-Stage Alcoholic Liver Disease

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Molecular imaging of NAD+‐dependent deacetylase SIRT1 in the brain

Cited by 4 publications

References 37 publications

Exercise coupled with calorie restriction reduces SIRT1 and SIRT2 in female obese adolescents

Exercise coupled with calorie restriction reduces SIRT1 and SIRT2 in female obese adolescents

Development and Characterization of a Novel Carbon-11 Labeled Positron Emission Tomography Radiotracer for Neuroimaging of Sirtuin 1 with Benzoxazine-Based Compounds

Noninvasive Positron Emission Tomography Imaging of SIRT1 in a Model of Early-Stage Alcoholic Liver Disease

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Molecular imaging of NAD⁺‐dependent deacetylase SIRT1 in the brain