SIRT4 antibody - middle region (ARP32451_P050)
- Known as:
- SIRT4 (anti-) - middle region (ARP32451_P050)
- Catalog number:
- arp32451_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- SIRT4 antibody - middle region (ARP32451_P050)
Related genes to: SIRT4 antibody - middle region (ARP32451_P050)
- Gene:
- SIRT4 NIH gene
- Name:
- sirtuin 4
- Previous symbol:
- -
- Synonyms:
- SIR2L4
- Chromosome:
- 12q24.31
- Locus Type:
- gene with protein product
- Date approved:
- 2001-03-20
- Date modifiied:
- 2014-11-19
Related products to: SIRT4 antibody - middle region (ARP32451_P050)
Related articles to: SIRT4 antibody - middle region (ARP32451_P050)
- Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, is characterized by progressive loss of dopaminergic neurons in the substantia nigra. Although the molecular mechanisms of PD remain incompletely understood, mitochondrial dysfunction has emerged as a central pathological driver, highlighting the urgent need for therapies targeting mitochondrial homeostasis. In this study, we demonstrate that rhynchophylline (Rhy), a bioactive alkaloid from species, exerts neuroprotective effects by restoring mitochondrial dynamics. Thermal proteome profiling identified dihydrolipoamide acetyltransferase (DLAT) as a direct target of Rhy. Genetic ablation of DLAT induced mitochondrial fragmentation and abolished Rhy-mediated beneficial effects on mitochondrial structure and function. Mechanically, Rhy binds to the N-terminal lipoyl domain of DLAT, allosterically disrupting its interaction with sirtuin 4 (SIRT4) and subsequently enhancing DLAT lipoylation, a critical post-translational modification for mitochondrial energy metabolism. , Rhy administration ameliorated motor deficits and dopaminergic neurodegeneration in both the 6-OHDA-induced and A53T -synuclein transgenic PD mouse models. Single-nucleus RNA sequencing further highlighted the clinical relevance of DLAT dysregulation in PD. Collectively, our findings establish Rhy as a promising PD therapeutic candidate and delineate DLAT as a pivotal node in therapeutic targets by promoting mitochondrial fusion and bioenergetics, offering a novel mechanistic avenue for neuroprotection. - Source: PubMed
Publication date: 2026/06/11
Liang XiaominYang XunfangWang ShuhuiZhuo FangfangHou XingziTu PengfeiLiu YangZeng KewuZhang Qingying - Sirtuins (SIRTs) are NAD-dependent enzymes implicated in cancer and other diseases, but the high conservation of their catalytic sites complicates the development of isoform-selective inhibitors. BZD9L1 is a benzimidazole-based sirtuin inhibitor with previously reported activity against SIRT1 and SIRT2. However, its potential interactions with other human sirtuin isoforms remain incompletely characterized. Here, we applied a comparative structure-based modelling framework integrating homology modelling, molecular docking, and targeted experimental assessment to investigate plausible binding modes of BZD9L1 across human SIRT1-7. Docking predicted that BZD9L1 could occupy the ADP-ribose cofactor-binding region of all seven isoforms, with broadly conserved orientations but differences in the predicted interaction networks. Hydrogen-bonding and π-mediated contacts predominated in the selected SIRT1-3 poses, whereas hydrophobic contacts were more apparent in several selected SIRT4-7 poses. The modest differences in docking scores were interpreted qualitatively and do not establish differential binding affinities or isoform selectivity. In colorectal cancer cells, BZD9L1 treatment altered acetyl-SOD2 levels, consistent with altered SIRT3-associated deacetylation in a cellular context. In a separate cell-free enzymatic assay, no measurable SIRT5 inhibition was detected under the conditions tested. These complementary assays provided distinct, independently interpreted readouts of SIRT3-associated cellular activity and SIRT5 enzymatic activity. Collectively, this study provides testable structural hypotheses regarding BZD9L1 recognition by human sirtuins and identifies interaction features that may guide subsequent biochemical and structure-based investigations. - Source: PubMed
Publication date: 2026/07/30
Tan Yi JerLee Yeuan TingOon Chern EinMancera Ricardo L - Myocardial ischemia-reperfusion injury (MIRI) is an inevitable pathological complication following reperfusion therapy for acute myocardial infarction. Massive reactive oxygen species burst, mitochondrial dysfunction, inflammatory cascade activation and multiple programmed cell death jointly aggravate irreversible cardiomyocyte loss, expanding infarct size and increasing the risk of progressive heart failure. As conserved NAD⁺-dependent deacetylases, the seven-member sirtuin (SIRT1-SIRT7) family exert widespread cardioprotective effects against MIRI, yet the subtype-specific molecular mechanisms, coordinated regulatory networks and translational bottlenecks lack systematic collation in existing reviews. This review aims to systematically summarize the regulatory pathways of all SIRT isoforms governing oxidative stress, mitochondrial homeostasis, inflammatory response and programmed cell death under MIRI, compare divergent biological functions among subtypes, sort out available SIRT-targeted pharmacological intervention strategies, and further clarify major obstacles restricting clinical translation, as well as prospective therapeutic targets for subsequent research. Distinguished by subcellular localization, nuclear, cytoplasmic and mitochondrial SIRT members participate in multi-layered myocardial defense. Nuclear SIRT1 coordinates AMPK-FOXO3-Nrf2 signaling to upregulate antioxidant enzymes and maintain mitophagic balance; mitochondrial SIRT3 dominates PINK1/Parkin-dependent mitophagy and deacetylates SOD2 to eliminate mitochondrial reactive oxygen species; cytoplasmic SIRT2 alleviates endoplasmic reticulum stress and restrains NLRP3 inflammasome activation; mitochondrial SIRT4 and SIRT5 stabilize mitochondrial fusion dynamics and eliminate lipid peroxidation via lysine desuccinylation, respectively; nuclear SIRT6 and SIRT7 relieve reperfusion inflammation, repair oxidative DNA damage and block late myocardial fibrosis. Collectively, the whole SIRT family forms an integrated endogenous protective network targeting all core pathological links of MIRI. In conclusion, SIRT1, SIRT3 and SIRT6 act as core cardioprotective subtypes: they synergistically activate the AMPK/Nrf2 antioxidant axis to block reperfusion oxidative injury. SIRT2, SIRT4, SIRT5 and SIRT7 serve auxiliary regulatory roles by balancing cardiac energy metabolism and maintaining genomic integrity. Current SIRT small-molecule agonists face prominent translational limitations including low oral bioavailability and poor myocardial tissue selectivity. Mitochondria or cardiomyocyte-targeted nano-delivery systems provide a feasible strategy to overcome such defects. Large animal MIRI models and prospective human clinical trials are urgently required to validate the long-term safety and therapeutic efficacy of SIRT-targeted interventions before clinical transformation. - Source: PubMed
Publication date: 2026/08/12
Xue TingtingWang ShuZhu XinyuLuo JialiZhu RuixiangLi HuihuiJu RuotongZhang PuhuaCui XiangrongJing Xuan - Sirtuins (SIRT1-SIRT7) are nicotinamide adenine dinucleotide (NAD) dependent deacylases that serves as metabolic sensors, coupling cellular energy status to chromatin structure, mitochondrial function, and stress responses. Dysregulated SIRT activity has been extensively studied in aging, metabolic syndrome, cardiovascular disease, neurodegeneration, cancer, and immune disorders. However, robust human evidence and SIRT-targeted therapies are lacking. Transgenic mouse models serve as key platforms to study gene function and guide therapeutic development. This review synthesizes evidence from transgenic mouse models regarding the core cellular processes governed by SIRTs: metabolism, genome integrity, stress resistance, immunity, and autophagy, and illustrates their operation across different organ systems. By comparing global, tissue-specific, and inducible knockout (KO) and overexpression (OE) models of cardiovascular, respiratory, digestive, nervous, endocrine, urogenital, musculoskeletal, malignant, and immune diseases, we identified central regulatory SIRTs (SIRT1, SIRT3, and SIRT6), context-dependent modifiers (SIRT2, SIRT4, SIRT5, and SIRT7), and their organ- and cell type-specific functions. We also summarize representative small-molecule SIRT activators, inhibitors, and degraders, covering both clinical and preclinical studies, and highlight where contradictions and knowledge gaps remain. Together, these analyses help clarify which aspects of SIRT modulation are most promising and under what isoform, tissue, and disease contexts they should be pursued for the development of SIRT‑targeted therapies in human disease. - Source: PubMed
Publication date: 2026/07/22
Wang Jia-YiJiang Feng-LiZhang Fang-YuanHuang Dong-HuiLi Xiao-YingGao SongYou HuaWu Qi-JunChen Huan-HuanGong Ting-Ting - - Source: PubMed
Publication date: 2026/07/22
Wu ZheqianGou KunxiangWang YongDai Lihua