Article
Biochemical Research Methods
Niels Boehnke, Markus Berger, Nils Griebenow, Antje Rottmann, Michael Erkelenz, Stefanie Hammer, Sandra Berndt, Judith Guenther, Antje M. Wengner, Beatrix Stelte-Ludwig, Christoph Mahlert, Simone Greven, Lisa Dietz, Hannah Jorissen, Naomi Barak, Ulf Boemer, Roman C. Hillig, Uwe Eberspaecher, Jorg Weiske, Anja Giese, Dominik Mumberg, Carl Friedrich Nising, Hilmar Weinmann, Anette Sommer
Summary: A new class of NAMPT inhibitors as ADC payloads was developed, optimizing their structures to create highly potent effector chemistries. The optimized NAMPTi-ADCs demonstrated potent in vivo antitumor efficacy with a very good selectivity profile.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Melika Ameli Mojarad, Mandana Ameli Mojarad, Alireza Pourmahdian
Summary: The study demonstrated that miR-26b can suppress the growth of breast cancer cells by downregulating NAMPT expression, NAD concentration, and cell viability, suggesting that miR-26b could be a promising target for breast cancer treatment.
DNA AND CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Melika Ameli Mojarad, Mandana Ameli Mojarad, Alireza Pourmahdian
Summary: This study highlights the significant tumor suppressor role of miR-26b in breast cancer, inhibiting cell growth and survival by targeting NAMPT and NAD levels. This makes miR-26b a promising target for breast cancer treatment.
DNA AND CELL BIOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Shiqi Luo, Juntao Zhao, Yangyang Zheng, Tao Chen, Zhiwen Wang
Summary: This article provides a detailed description of the two biosynthetic pathways of NMN and introduces the latest studies on NMN production through different pathways using metabolic engineering strategies. NMN accumulation can be improved by optimizing the activity of key enzymes, enhancing the supply of precursors and co-factors, inhibiting the synthesis of byproducts, and promoting product export. Finally, the current challenges of producing NMN and possible solutions for the future are discussed.
FERMENTATION-BASEL
(2023)
Review
Pharmacology & Pharmacy
Yumeng Zhu, Ping Xu, Xuan Huang, Wen Shuai, Li Liu, Shuai Zhang, Rui Zhao, Xiuying Hu, Guan Wang
Summary: Nicotinamide phosphoribosyltransferase (NAMPT) plays a significant role in mammals by synthesizing nicotinamide mononucleotide (NMN) for metabolic homeostasis and cell survival, serving as a key protein in the host's defense mechanism. Neurodegenerative diseases pose a serious threat to human health, but effective drugs are limited. NAMPT has active biological functions in neurogenesis, making it a powerful therapeutic target for neurodegenerative diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Public, Environmental & Occupational Health
Xu Sun, Lide Su, Te Bu, Yang Zhang
Summary: Aging is associated with decreased NAD levels, which can lead to dysfunctional mitochondria and indirectly affect various diseases. This meta-analysis examined the effect of exercise training on the expression of iNAMPT, a central enzyme in NAD synthesis, in humans.
FRONTIERS IN PUBLIC HEALTH
(2023)
Article
Chemistry, Medicinal
Junfei Cheng, Shipeng He, Jun Xu, Min Huang, Guoqiang Dong, Chunquan Sheng
Summary: Proteolysis-targeting chimera (PROTAC) is a promising technology in targeted protein degradation and drug discovery. This study designed the first fluorescent and theranostic PROTACs for real-time imaging of the degradation of nicotinamide phosphoribosyltransferase (NAMPT) in living cells. The results showed efficient degradation of NAMPT and significant reduction of nicotinamide adenine dinucleotide (NAD(+)), leading to potent antitumor activities in vitro and in vivo. This proof-of-concept study provides a new strategy for real-time visualization of protein degradation and improvement of diagnosis and therapeutic efficacy of PROTACs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Yongxian Zhuang, Allison B. B. Haugrud, Meg A. A. Schaefer, Shanta M. M. Messerli, W. Keith Miskimins
Summary: Depletion of cellular NAD+ is a critical factor in the sensitivity of cancer cells to the cytotoxic effects of metformin. NAMPT plays a key role in maintaining sufficient levels of NAD+, and cancer cells that express elevated levels of NAMPT are resistant to metformin's killing effect.
FRONTIERS IN ONCOLOGY
(2023)
Article
Obstetrics & Gynecology
Priscila R. Nunes, Ricardo C. Cavalli, Vanessa A. Belo, Valeria C. Sandrim, Marcelo R. Luizon
Summary: This study conducted the first longitudinal study of plasma visfatin levels in healthy pregnant women, finding that visfatin levels were significantly higher in the third trimester compared to the second trimester, and significantly reduced in the postpartum period. These findings suggest the potential of visfatin as a biomarker for pregnancy complications.
REPRODUCTIVE SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Yichen Wei, Haotian Xiang, Wenqiu Zhang
Summary: NAMPT is an overexpressed rate-limiting enzyme in several types of cancers, impacting the NAD and NADPH pool. NAMPT inhibitors have shown significant anti-tumor efficacy, but early clinical trials have had limited results, requiring additional strategies for improvement.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Xiaoqun Lv, Jinguo Zhang, Jun Zhang, Wencai Guan, Weifang Ren, Yujuan Liu, Guoxiong Xu
Summary: NAMPT is overexpressed in colorectal cancer (CRC) and associated with short overall survival. It promotes the protein expression levels of components in the transforming growth factor-beta (TGF-beta) signaling pathway and TGF-beta 1 secretion. Treatment with TGF-beta 1 down-regulates NAMPT expression in CRC cells, partly through up-regulation of miR-1-3p that directly binds to the NAMPT 3'-UTR.
ONCOTARGETS AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Shahin Alizadeh-Fanalou, Saman Hosseinkhani, Ali Nazarizadeh, Samira Ezzati-Mobaser, Zahra Hesari, Parisa Aziminezhadan, Zohreh Abdolvahabi, Meysam Abolmaali, Masoumeh Tavakoli-Yaraki, Mitra Nourbakhsh
Summary: Targeting the NAMPT-mediated NAD salvage pathway by miR-613 is a novel approach for managing breast cancer, which is worth further investigation.
DNA AND CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yaling Xu, Lijia Yu, Ying Liu, Xiaohui Tang, Xijin Wang
Summary: NAMPT could be a promising target for microglia modulation, and NAMPT inhibition may attenuate microglial inflammation.
NEUROCHEMICAL RESEARCH
(2021)
Review
Nutrition & Dietetics
Taichi Nagahisa, Shotaro Kosugi, Shintaro Yamaguchi
Summary: The intestine, particularly its NAMPT-mediated NAD(+) biosynthesis pathway, plays a crucial role in regulating intestinal homeostasis and GLP-1 secretion. Boosting the intestinal AMPK-NAMPT-NAD(+)-SIRT pathway has gained attention as a novel strategy to improve impaired glucose tolerance. This review explores the regulatory mechanisms and importance of intestinal NAMPT-mediated NAD(+) biosynthesis in obesity and aging, and discusses the potential therapeutic strategies for postprandial glucose dysregulation.
Article
Neurosciences
Chen Shen, Cong Chen, Tong Wang, Tong-Yao Gao, Min Zeng, Yun-Bi Lu, Wei-Ping Zhang
Summary: Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme in the salvaging synthesis pathway of nicotinamide adenine dinucleotide (NAD). Depletion of NAMPT can lead to cognitive deficiency in hippocampus neurons and increase the risk of neurodegeneration due to mitochondrial dysfunction.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Magdalena Nikolaeva-Koleva, Laura Butron, Sara Gonzalez-Rodriguez, Isabel Devesa, Pierluigi Valente, Marta Serafini, Armando A. Genazzani, Tracey Pirali, Gregorio Fernandez Ballester, Asia Fernandez-Carvajal, Antonio Ferrer-Montiel
Summary: TRPV1 modulators like AG1529 competitively block capsaicin-induced activation of TRPV1, reducing neuronal firing and showing potential as a topical anti-pruritic and anti-inflammatory medication.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Silvio Aprile, Beatrice Riva, Irene Preet Bhela, Celia Cordero-Sanchez, Giulia Avino, Armando A. Genazzani, Marta Serafini, Tracey Pirali
Summary: The study focused on a bioisosteric replacement strategy in pyrazole derivatives to improve metabolic stability of SOCE modulators. A compound identified among the derivatives was found to increase calcium entry, thereby expanding the library of available SOCE activators.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Review
Biochemistry & Molecular Biology
Jose Cesar Rosa Neto, Philip C. Calder, Rui Curi, Philip Newsholme, Jaswinder K. Sethi, Loreana S. Silveira
Summary: Macrophages and lymphocytes exhibit metabolic plasticity, influenced by their activation state and the availability of energy substrates. Fatty acids play a crucial role in governing the phenotype, activation, and functional status of these cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Nutrition & Dietetics
Josh Bilson, Jaswinder K. Sethi, Christopher D. Byrne
Summary: NAFLD is a multi-system disease that affects organs beyond the liver, with risk influenced by age and gender, as well as changes in white adipose tissue and intestinal function.
PROCEEDINGS OF THE NUTRITION SOCIETY
(2022)
Article
Oncology
Annamaria Antona, Marco Varalda, Konkonika Roy, Francesco Favero, Eleonora Mazzucco, Miriam Zuccala, Giovanni Leo, Giulia Soggia, Valentina Bettio, Martina Tosi, Miriam Gaggianesi, Beatrice Riva, Simone Reano, Armando Genazzani, Marcello Manfredi, Giorgio Stassi, Davide Cora, Sandra D'Alfonso, Daniela Capello
Summary: Despite advancements in treatments, half of colorectal cancer (CRC) patients still die from recurrence and metastatic disease, necessitating novel therapeutic approaches. Drug repurposing is gaining interest as a faster and cost-effective alternative to new drug synthesis. Psychiatric medications show promise in treating CRC. Study demonstrates the potential of the antipsychotic drug spiperone in inducing apoptosis in CRC cells by targeting unique pathways.
Article
Cell Biology
Giulia Dematteis, Elena Restelli, Virginia Vita Vanella, Marcello Manfredi, Emilio Marengo, Marco Corazzari, Armando A. Genazzani, Roberto Chiesa, Dmitry Lim, Laura Tapella
Summary: The genetic ablation or pharmacological inhibition of the calcium-activated phosphatase calcineurin (CaN) in astrocytes reduces PrP(C) expression, providing new insights into the regulation of PrP expression in astrocytes and suggesting the therapeutic potential of astroglial cells.
Article
Medicine, General & Internal
Federico Villa, Aurora Di Filippo, Andrea Pierantozzi, Armando Genazzani, Antonio Addis, Gianluca Trifiro, Agnese Cangini, Giovanni Tafuri, Daniela Settesoldi, Francesco Trotta
Summary: This study analyzed the prices of orphan drugs and their correlation with the epidemiology of rare diseases in Italy from 2014 to 2019. The results showed that the price of orphan drugs is not influenced by the rarity of the disease, and the sales volume does not correlate with the epidemiology or therapy cost.
FRONTIERS IN MEDICINE
(2022)
Article
Multidisciplinary Sciences
Giorgia Colombo, Cristina Travelli, Chiara Porta, Armando A. Genazzani
Summary: This article investigates the effects of eNAMPT on macrophage-driven inflammation. The study finds that eNAMPT triggers an M1-skewed transcriptional program and selectively boosts IFN gamma-driven transcriptional activation via STAT1/3 phosphorylation. Furthermore, the secretion of eNAMPT promotes the chemotactic recruitment of myeloid cells, creating a positive feedback loop for inflammation. The research also reveals the involvement of receptors other than the recognized TLR4 receptor.
Article
Cell Biology
Beatrice Riva, Emanuela Pessolano, Edoardo Quaglia, Celia Cordero-Sanchez, Irene P. Bhela, Ana Topf, Marta Serafini, Daniel Cox, Elizabeth Harris, Matteo Garibaldi, Rita Barresi, Tracey Pirali, Armando A. Genazzani
Summary: Gain-of-function mutations on STIM1 and ORAI1 genes lead to increased calcium entry into cells, causing a range of symptoms related to muscle weakness and cramps in ultra-rare genetic disorders. Pharmacological intervention targeting these mutations has entered clinical trials with tolerability demonstrated. Research has shown that all tested mutations, except one, can be inhibited, providing a potential avenue for developing treatments for tubular aggregate myopathies.
Article
Environmental Sciences
Elisabetta Galai, Lorenza Scotti, Marco Gilardetti, Andrealuna Ucciero, Daniela Ferrante, Elisabetta Poluzzi, Armando A. Genazzani, Francesco Barone-Adesi
Summary: Adverse drug reactions (ADRs) are a major health problem among the elderly population, largely due to polypharmacy and the resulting drug-drug interactions (DDIs). In this study, the prevalence of selected DDIs among elderly outpatients was analyzed over a six-year period. The results showed a decreasing trend in the prevalence of most DDIs, with some exceptions. The complexity of drug formularies and prescribing practices highlight the need for updated DDI lists to monitor drug appropriateness and reduce ADRs.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Article
Hematology
Celia Cordero-Sanchez, Emanuela Pessolano, Beatrice Riva, Mauro Vismara, Silvia Maria Grazia Trivigno, Nausicaa Clemente, Silvio Aprile, Federico Alessandro Ruffinatti, Paola Portararo, Nicoletta Filigheddu, Ivan Zaggia, Irene P. Bhela, Marta Serafini, Tracey Pirali, Mario P. Colombo, Mauro Torti, Sabina Sangaletti, Alessandra Bertoni, Armando A. Genazzani
Summary: Store-operated Ca2+-entry is a cellular mechanism associated with ultra-rare diseases. In a mouse model with the STIM1 p.I115F mutation, it was found that CIC-39Na can restore platelet number and counteract abnormal bleeding, providing a new pharmacological treatment strategy for thrombocytopenia in these diseases.
Review
Endocrinology & Metabolism
Josh Bilson, Jaswinder K. Sethi, Christopher D. Byrne
Summary: This review discusses the recent evidence of distinct white adipocyte subpopulations in white adipose tissue and how these subpopulations may be altered with increasing adiposity and/or metabolic disease. Studies have shown that these subtypes are potentially functionally distinct and may play different roles in white adipose tissue function and obesity-associated metabolic diseases.
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
(2023)
Article
Endocrinology & Metabolism
Jaswinder K. Sethi, Gokhan S. Hotamisligil
Summary: This review focuses on tumor necrosis factor (TNF) in the context of metabolic inflammation, highlighting its immunometabolic actions and relevance to other pro-inflammatory signals and metabolic diseases. It presents a conceptual framework applicable to the complex network of pro-inflammatory signals and their integration with metabolic regulation.
Meeting Abstract
Endocrinology & Metabolism
J. Bilson, E. Scorletti, L. B. Bindels, P. R. Afolabi, G. Targher, P. C. Calder, J. K. Sethi, C. D. Byrne
Meeting Abstract
Endocrinology & Metabolism
J. Bilson, E. Scorletti, L. B. Bindels, P. R. Afolabi, G. Targher, P. C. Calder, J. K. Sethi, C. D. Byrne
