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An Y, Guo C, Wang X, Liu J, Li Z, Ding J, Zhang Q, Zhou H, Xia B, Wang J, Yu Y, Wan C, Wang J, Dai J. USP18 Promotes Cholesterol Efflux and Mitigates Atherosclerosis by Deubiquitinating ABCG1. J Cell Mol Med 2025; 29:e70320. [PMID: 39804798 PMCID: PMC11728483 DOI: 10.1111/jcmm.70320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 12/11/2024] [Accepted: 12/13/2024] [Indexed: 01/16/2025] Open
Abstract
Deubiquitinating enzymes (DUBs) are integral regulators of protein stability. Among these, Ubiquitin-specific protease 18 (USP18) has emerged as a potential therapeutic target for heart failure. However, its precise role in atherosclerosis remains to be comprehensively understood. This study endeavours to examine the impact of USP18 on atherosclerosis and elucidate its corresponding molecular mechanisms. Our studies indicate an elevated expression of USP18 in human coronary atherosclerotic plaques. Notably, the knockdown of USP18 significantly exacerbated lipid accumulation in macrophages. This knockdown effect impaired cholesterol efflux and influenced the downregulation of ATP-binding cassette transporter G1 (ABCG1) expression, achieved by altering the ubiquitination level of ABCG1. Comprehensive mechanistic studies unveiled that USP18 directly affiliates with ABCG1, reducing its ubiquitination and consequently bolstering ABCG1 stability within macrophages. Furthermore, in vivo studies elucidated that the knockdown of USP18 notably elevated atherosclerotic lesions and diminished ABCG1 levels in the plaques of Apoe-/- mice. In summary, our results suggested that USP18 plays a crucial role in managing the progression of atherosclerosis by strengthening the expression of ABCG1 protein through its deubiquitinating effect on ABCG1.
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Affiliation(s)
- Yang An
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Chuxian Guo
- Department of CardiologyThe First Affiliated Hospital of Jinan UniversityGuangzhouChina
| | - Xiaoli Wang
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Jiangjin Liu
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Zhu Li
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Jiuyang Ding
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Qiaojun Zhang
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Hongmei Zhou
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Bing Xia
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Jiawen Wang
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Yanni Yu
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Changwu Wan
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Jie Wang
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
| | - Jialin Dai
- School of Forensic MedicineGuizhou Medical UniversityGuiyangChina
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Urakov AL, Tyurin AV, Shchekin VS, Siddikov OA, Abdurakhmonov IR, Gabdrakhimova RA, Samorodov AV. Ubiquitylation in the development of somatic diseases: a mechanism of cellular regulation and a new therapeutic target. REVIEWS ON CLINICAL PHARMACOLOGY AND DRUG THERAPY 2024; 22:339-349. [DOI: 10.17816/rcf631847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2025]
Abstract
At the present stage of medical science, an increasing role in the pathogenesis of various groups of diseases is assigned to the mechanisms of epigenetic regulation and posttranslational modifications of proteins. One of these mechanisms is ubiquitylation, which is able to regulate the functional activity of proteins, their stability, and also influence the processes of cell death. Involvement in a large number of metabolic pathways and presently identified associations with oncological, cardiovascular, neurological, and inflammatory diseases makes ubiquitylation of the enzymes involved a promising target to develop new therapy options. In this review, we consider the effect of ubiquitination on the development of diseases of the cardiovascular, nervous systems, diabetes mellitus, as well as the development of possible treatment options.
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Wan Q, Lu Q, Luo S, Guan C, Zhang H. The beneficial health effects of puerarin in the treatment of cardiovascular diseases: from mechanisms to therapeutics. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:7273-7296. [PMID: 38709267 DOI: 10.1007/s00210-024-03142-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 05/02/2024] [Indexed: 05/07/2024]
Abstract
Cardiovascular diseases (CVDs) are the leading causes of death globally that seriously threaten human health. Although novel western medicines have continued to be discovered over the past few decades to inhibit the progression of CVDs, new drug research and development for treating CVDs with less side effects and adverse reactions are continuously being desired. Puerarin is a natural product found in a variety of medicinal plants belonging to the flavonoid family with potent biological and pharmacological activities. Abundant research findings in the literature have suggested that puerarin possesses a promising prospect in treating CVDs. In recent years, numerous new molecular mechanisms of puerarin have been explored in experimental and clinical studies, providing new evidence for this plant metabolite to protect against CVDs. This article systematically introduces the history of use, bioavailability, and various dosage forms of puerarin and further summarizes recently published data on the major research advances and their underlying therapeutic mechanisms in treating CVDs. It may provide references for researchers in the fields of pharmacology, natural products, and internal medicine.
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Affiliation(s)
- Qiang Wan
- Affiliated Hospital of Jiangxi University of Chinese Medicine, 445 Bayi Avenue, Nanchang, 330006, China.
- Clinical Medical College, Jiangxi University of Chinese Medicine, 445 Bayi Avenue, Nanchang, 330006, China.
| | - Qiwen Lu
- Graduate School, Jiangxi University of Chinese Medicine, 1688 Meiling Avenue, Nanchang, 330004, China
| | - Sang Luo
- Graduate School, Jiangxi University of Chinese Medicine, 1688 Meiling Avenue, Nanchang, 330004, China
| | - Chengyan Guan
- Graduate School, Jiangxi University of Chinese Medicine, 1688 Meiling Avenue, Nanchang, 330004, China
| | - Hao Zhang
- Graduate School, Jiangxi University of Chinese Medicine, 1688 Meiling Avenue, Nanchang, 330004, China
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Huang J, Zhu Z, Schlüter D, Lambertsen KL, Song W, Wang X. Ubiquitous regulation of cerebrovascular diseases by ubiquitin-modifying enzymes. Clin Transl Med 2024; 14:e1719. [PMID: 38778460 PMCID: PMC11111633 DOI: 10.1002/ctm2.1719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 05/06/2024] [Accepted: 05/11/2024] [Indexed: 05/25/2024] Open
Abstract
Cerebrovascular diseases (CVDs) are a major threat to global health. Elucidation of the molecular mechanisms underlying the pathology of CVDs is critical for the development of efficacious preventative and therapeutic approaches. Accumulating studies have highlighted the significance of ubiquitin-modifying enzymes (UMEs) in the regulation of CVDs. UMEs are a group of enzymes that orchestrate ubiquitination, a post-translational modification tightly involved in CVDs. Functionally, UMEs regulate multiple pathological processes in ischemic and hemorrhagic stroke, moyamoya disease, and atherosclerosis. Considering the important roles of UMEs in CVDs, they may become novel druggable targets for these diseases. Besides, techniques applying UMEs, such as proteolysis-targeting chimera and deubiquitinase-targeting chimera, may also revolutionize the therapy of CVDs in the future.
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Affiliation(s)
- Jingyong Huang
- Department of Vascular SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Zhenhu Zhu
- School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhouChina
| | - Dirk Schlüter
- Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical SchoolHannoverGermany
| | - Kate Lykke Lambertsen
- Department of Neurobiology ResearchInstitute of Molecular MedicineUniversity of Southern DenmarkOdense CDenmark
- BRIGDE—Brain Research—Inter‐Disciplinary Guided Excellence, Department of Clinical ResearchUniversity of Southern DenmarkOdense CDenmark
- Department of NeurologyOdense University HospitalOdense CDenmark
| | - Weihong Song
- Oujiang LaboratoryKey Laboratory of Alzheimer's Disease of Zhejiang ProvinceZhejiang Provincial Clinical Research Center for Mental DisordersInstitute of AgingSchool of Mental HealthAffiliated Kangning HospitalThe Second Affiliated HospitalYuying Children's HospitalWenzhou Medical UniversityWenzhouChina
| | - Xu Wang
- School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhouChina
- Oujiang LaboratoryKey Laboratory of Alzheimer's Disease of Zhejiang ProvinceZhejiang Provincial Clinical Research Center for Mental DisordersInstitute of AgingSchool of Mental HealthAffiliated Kangning HospitalThe Second Affiliated HospitalYuying Children's HospitalWenzhou Medical UniversityWenzhouChina
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Chen R, Zhang H, Li L, Li J, Xie J, Weng J, Tan H, Liu Y, Guo T, Wang M. Roles of ubiquitin-specific proteases in inflammatory diseases. Front Immunol 2024; 15:1258740. [PMID: 38322269 PMCID: PMC10844489 DOI: 10.3389/fimmu.2024.1258740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 01/02/2024] [Indexed: 02/08/2024] Open
Abstract
Ubiquitin-specific proteases (USPs), as one of the deubiquitinating enzymes (DUBs) families, regulate the fate of proteins and signaling pathway transduction by removing ubiquitin chains from the target proteins. USPs are essential for the modulation of a variety of physiological processes, such as DNA repair, cell metabolism and differentiation, epigenetic modulations as well as protein stability. Recently, extensive research has demonstrated that USPs exert a significant impact on innate and adaptive immune reactions, metabolic syndromes, inflammatory disorders, and infection via post-translational modification processes. This review summarizes the important roles of the USPs in the onset and progression of inflammatory diseases, including periodontitis, pneumonia, atherosclerosis, inflammatory bowel disease, sepsis, hepatitis, diabetes, and obesity. Moreover, we highlight a comprehensive overview of the pathogenesis of USPs in these inflammatory diseases as well as post-translational modifications in the inflammatory responses and pave the way for future prospect of targeted therapies in these inflammatory diseases.
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Affiliation(s)
- Rui Chen
- Center of Obesity and Metabolic Diseases, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
- Department of Stomatology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
- College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Hui Zhang
- College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China
- College of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Linke Li
- Center of Obesity and Metabolic Diseases, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
- Department of Stomatology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Jinsheng Li
- College of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Jiang Xie
- Department of Pediatrics, Chengdu Third People's Hospital, Chengdu, Sichuan, China
| | - Jie Weng
- College of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Huan Tan
- Center of Obesity and Metabolic Diseases, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
- College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Yanjun Liu
- Center of Obesity and Metabolic Diseases, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
- College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Tailin Guo
- Center of Obesity and Metabolic Diseases, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
- College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Mengyuan Wang
- Center of Obesity and Metabolic Diseases, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
- Department of Stomatology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
- College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China
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Jing J, Guo J, Dai R, Zhu C, Zhang Z. Targeting gut microbiota and immune crosstalk: potential mechanisms of natural products in the treatment of atherosclerosis. Front Pharmacol 2023; 14:1252907. [PMID: 37719851 PMCID: PMC10504665 DOI: 10.3389/fphar.2023.1252907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 08/21/2023] [Indexed: 09/19/2023] Open
Abstract
Atherosclerosis (AS) is a chronic inflammatory reaction that primarily affects large and medium-sized arteries. It is a major cause of cardiovascular disease and peripheral arterial occlusive disease. The pathogenesis of AS involves specific structural and functional alterations in various populations of vascular cells at different stages of the disease. The immune response is involved throughout the entire developmental stage of AS, and targeting immune cells presents a promising avenue for its treatment. Over the past 2 decades, studies have shown that gut microbiota (GM) and its metabolites, such as trimethylamine-N-oxide, have a significant impact on the progression of AS. Interestingly, it has also been reported that there are complex mechanisms of action between GM and their metabolites, immune responses, and natural products that can have an impact on AS. GM and its metabolites regulate the functional expression of immune cells and have potential impacts on AS. Natural products have a wide range of health properties, and researchers are increasingly focusing on their role in AS. Now, there is compelling evidence that natural products provide an alternative approach to improving immune function in the AS microenvironment by modulating the GM. Natural product metabolites such as resveratrol, berberine, curcumin, and quercetin may improve the intestinal microenvironment by modulating the relative abundance of GM, which in turn influences the accumulation of GM metabolites. Natural products can delay the progression of AS by regulating the metabolism of GM, inhibiting the migration of monocytes and macrophages, promoting the polarization of the M2 phenotype of macrophages, down-regulating the level of inflammatory factors, regulating the balance of Treg/Th17, and inhibiting the formation of foam cells. Based on the above, we describe recent advances in the use of natural products that target GM and immune cells crosstalk to treat AS, which may bring some insights to guide the treatment of AS.
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Affiliation(s)
- Jinpeng Jing
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jing Guo
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Rui Dai
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chaojun Zhu
- Institute of TCM Ulcers, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Surgical Department of Traditional Chinese Medicine, Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhaohui Zhang
- Institute of TCM Ulcers, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Surgical Department of Traditional Chinese Medicine, Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Wang ZQ, Yao HP, Sun Z. N ε-(carboxymethyl)lysine promotes lipid uptake of macrophage via cluster of differentiation 36 and receptor for advanced glycation end products. World J Diabetes 2023; 14:222-233. [PMID: 37035231 PMCID: PMC10075039 DOI: 10.4239/wjd.v14.i3.222] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 01/08/2023] [Accepted: 02/15/2023] [Indexed: 03/15/2023] Open
Abstract
BACKGROUND Advanced glycation end products (AGEs) are diabetic metabolic toxic products that cannot be ignored. Nε-(carboxymethyl)lysine (CML), a component of AGEs, could increase macrophage lipid uptake, promote foam cell formation, and thereby accelerate atherosclerosis. The receptor for AGEs (RAGE) and cluster of differentiation 36 (CD36) were the receptors of CML. However, it is still unknown whether RAGE and CD36 play key roles in CML-promoted lipid uptake.
AIM Our study aimed to explore the role of RAGE and CD36 in CML-induced mac-rophage lipid uptake.
METHODS In this study, we examined the effect of CML on lipid uptake by Raw264.7 macrophages. After adding 10 mmol/L CML, the lipid accumulation in macro-phages was confirmed by oil red O staining. Expression changes of CD36 and RAGE were detected with immunoblotting and quantitative real-time polymerase chain reaction. The interaction between CML with CD36 and RAGE was verified by immunoprecipitation. We synthesized a novel N-succinimidyl-4-18F-fluorobenzoate-CML radioactive probe. Radioactive receptor-ligand binding assays were performed to test the binding affinity between CML with CD36 and RAGE. The effects of blocking CD36 or RAGE on CML-promoting lipid uptake were also detected.
RESULTS The study revealed that CML significantly promoted lipid uptake by macro-phages. Immunoprecipitation and radioactive receptor-ligand binding assays indicated that CML could specifically bind to both CD36 and RAGE. CML had a higher affinity for CD36 than RAGE. ARG82, ASN71, and THR70 were the potential interacting amino acids that CD36 binds to CML Anti-CD36 and anti-RAGE could block the uptake of CML by macrophages. The lipid uptake promotion effect of CML was significantly attenuated after blocking CD36 or RAGE.
CONCLUSION Our results suggest that the binding of CML with CD36 and RAGE promotes macrophage lipid uptake.
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Affiliation(s)
- Zhong-Qun Wang
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
| | - Hai-Peng Yao
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
| | - Zhen Sun
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
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Tao L, Liu X, Jiang X, Zhang K, Wang Y, Li X, Jiang S, Han T. USP10 as a Potential Therapeutic Target in Human Cancers. Genes (Basel) 2022; 13:genes13050831. [PMID: 35627217 PMCID: PMC9142050 DOI: 10.3390/genes13050831] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 04/28/2022] [Accepted: 05/04/2022] [Indexed: 12/04/2022] Open
Abstract
Deubiquitination is a major form of post-translational protein modification involved in the regulation of protein homeostasis and various cellular processes. Deubiquitinating enzymes (DUBs), comprising about five subfamily members, are key players in deubiquitination. USP10 is a USP-family DUB featuring the classic USP domain, which performs deubiquitination. Emerging evidence has demonstrated that USP10 is a double-edged sword in human cancers. However, the precise molecular mechanisms underlying its different effects in tumorigenesis remain elusive. A possible reason is dependence on the cell context. In this review, we summarize the downstream substrates and upstream regulators of USP10 as well as its dual role as an oncogene and tumor suppressor in various human cancers. Furthermore, we summarize multiple pharmacological USP10 inhibitors, including small-molecule inhibitors, such as spautin-1, and traditional Chinese medicines. Taken together, the development of specific and efficient USP10 inhibitors based on USP10’s oncogenic role and for different cancer types could be a promising therapeutic strategy.
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Affiliation(s)
- Li Tao
- The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China;
| | - Xiao Liu
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China; (X.L.); (X.J.); (K.Z.); (Y.W.)
| | - Xinya Jiang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China; (X.L.); (X.J.); (K.Z.); (Y.W.)
| | - Kun Zhang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China; (X.L.); (X.J.); (K.Z.); (Y.W.)
| | - Yijing Wang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China; (X.L.); (X.J.); (K.Z.); (Y.W.)
| | - Xiumin Li
- Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang Medical University, Xinxiang 453003, China;
| | - Shulong Jiang
- Clinical Medical Laboratory Center, Jining First People’s Hospital, Jining Medical University, Jining 272000, China
- Correspondence: (S.J.); (T.H.)
| | - Tao Han
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China; (X.L.); (X.J.); (K.Z.); (Y.W.)
- Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang Medical University, Xinxiang 453003, China;
- Correspondence: (S.J.); (T.H.)
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Karunakaran U, Elumalai S, Moon JS, Won KC. CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting. Cells 2021; 10:cells10071833. [PMID: 34360006 PMCID: PMC8305429 DOI: 10.3390/cells10071833] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/14/2021] [Accepted: 07/17/2021] [Indexed: 12/24/2022] Open
Abstract
The cluster of differentiation 36 (CD36) is a scavenger receptor present on various types of cells and has multiple biological functions that may be important in inflammation and in the pathogenesis of metabolic diseases, including diabetes. Here, we consider recent insights into how the CD36 response becomes deregulated under metabolic conditions, as well as the therapeutic benefits of CD36 inhibition, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with metabolic diseases. To facilitate this process further, it is important to pinpoint regulatory mechanisms that are relevant under physiological and pathological conditions. In particular, understanding the mechanisms involved in dictating specific CD36 downstream cellular outcomes will aid in the discovery of potent compounds that target specific CD36 downstream signaling cascades.
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Affiliation(s)
- Udayakumar Karunakaran
- Innovative Center for Aging Research, Yeungnam University Medical Center, Daegu 42415, Korea; (U.K.); (S.E.)
| | - Suma Elumalai
- Innovative Center for Aging Research, Yeungnam University Medical Center, Daegu 42415, Korea; (U.K.); (S.E.)
| | - Jun-Sung Moon
- Innovative Center for Aging Research, Yeungnam University Medical Center, Daegu 42415, Korea; (U.K.); (S.E.)
- Yeungnam University College of Medicine, Daegu 42415, Korea
- Correspondence: (J.-S.M.); (K.-C.W.); Tel.: +82-53-620-3825 (J.-S.M.); +82-53-620-3846 (K.-C.W.)
| | - Kyu-Chang Won
- Innovative Center for Aging Research, Yeungnam University Medical Center, Daegu 42415, Korea; (U.K.); (S.E.)
- Yeungnam University College of Medicine, Daegu 42415, Korea
- Correspondence: (J.-S.M.); (K.-C.W.); Tel.: +82-53-620-3825 (J.-S.M.); +82-53-620-3846 (K.-C.W.)
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