Review
Biochemistry & Molecular Biology
Renata Novak Kujundzic, Marin Prpic, Nikola Dakovic, Nina Dabelic, Marko Tomljanovic, Anamarija Mojzes, Ana Frobe, Koraljka Gall Troselj
Summary: Overexpression and activity of NNMT in cancer can disrupt NAD(+) homeostasis and reduce cellular methylation potential. The inhibitory effect of 2-PY on PARP-1 activity, which cancels out NNMT's positive effect on cellular NAD(+) flux, is often overlooked.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Wanfeng Xu, Ling Hou, Ping Li, Ling Li
Summary: The interference of NNMT expression was found to reduce lipid accumulation and triglyceride content, as well as decrease the expression of certain genes and proteins related to lipid metabolism. This suggests that NNMT plays an important role in the function and metabolism of adipocytes.
Review
Endocrinology & Metabolism
Annalisa Roberti, Agustin F. Fernandez, Mario F. Fraga
Summary: NNMT acts as a key link between cellular metabolism and epigenetic gene regulation, playing a central role in various pathologies. Targeting NNMT pathways represents a current pharmaceutical challenge for treating a range of metabolic-related diseases and cancers.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Aimo Kannt, Sridharan Rajagopal, Mahanandeesha S. Hallur, Indu Swamy, Rajendra Kristam, Saravanakumar Dhakshinamoorthy, Joerg Czech, Gernot Zech, Herman Schreuder, Sven Ruf
Summary: Nicotinamide-N-methyltransferase (NNMT) is a cytosolic enzyme that catalyzes the transfer of a methyl group from S-adenosyl-methionine (SAM) to nicotinamide (Nam). Its expression in various tissues has been linked to metabolic diseases, and potent small molecule inhibitors with different binding modes have been identified through X-ray crystallographic studies.
Article
Oncology
Roberto Campagna, Eleonora Salvolini, Veronica Pompei, Valentina Pozzi, Alessia Salvucci, Elisa Molinelli, Valerio Brisigotti, Davide Sartini, Anna Campanati, Annamaria Offidani, Monica Emanuelli
Summary: Melanoma, despite its small proportion of all skin tumors, is a major contributor to skin cancer-related deaths. This study identified NNMT enzyme as a potential therapeutic target for melanoma treatment, demonstrating that reducing NNMT levels can significantly inhibit cell proliferation and migration, as well as enhance sensitivity to chemotherapy drugs in melanoma cells.
PIGMENT CELL & MELANOMA RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Roberto Campagna, Lukasz Mateuszuk, Kamila Wojnar-Lason, Patrycja Kaczara, Anna Tworzydlo, Agnieszka Kij, Robert Bujok, Jacek Mlynarski, Yu Wang, Davide Sartini, Monica Emanuelli, Stefan Chlopicki
Summary: Nicotinamide N-methyltransferase (NNMT) plays an important role in endothelial cells by regulating cell viability, possibly through the modulation of SIRT1 expression levels under oxidative stress insult.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Oksana Stepinska, Dorota Dymkowska, Lukasz Mateuszuk, Krzysztof Zablocki
Summary: This study aimed to investigate the potential role of nicotinamide N-methyltransferase in the metabolic response of human aortic endothelial cells. The findings suggest that this enzyme may affect NAD(+) synthesis and epigenetic modifications of chromatin by regulating intracellular nicotinamide and S-adenosylmethionine levels. The specific metabolic role of nicotinamide N-methyltransferase in vascular endothelium is still unclear and further research is needed.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Weixian Zhang, Yue Jing, Shuai Wang, Yan Wu, Yawei Sun, Jia Zhuang, Xiaofeng Huang, Sheng Chen, Xiaoxin Zhang, Yuxian Song, Qingang Hu, Yanhong Ni
Summary: This study revealed that NNMT may serve as a critical regulator of EMT in oral squamous cell carcinoma (OSCC) and could be a prognostic biomarker for OSCC patients. These findings provide novel insights for future research in NNMT-targeted OSCC metastasis and recurrence therapy.
Article
Oncology
Jun Yang, Qingchao Tong, Ying Zhang, Shijin Yuan, Yuzhen Gao, Ke Deng, Yanzhong Wang, Jie Lu, Xinyou Xie, Zhe Zhang, Jun Zhang
Summary: This study investigated the distribution of NNMT expression in CRC and found that its overexpression was associated with unfavorable clinical characteristics and survival outcomes. Particularly, high NNMT expression in tumor stroma cells was strongly correlated with metastasis and poor survival in CRC patients. Functional experiments demonstrated that stromal cells with high NNMT expression secreted 1-MAN to promote migration and invasion of CRC cells. Overall, NNMT may serve as a potential prognostic indicator in CRC patients.
Article
Food Science & Technology
Aimei Liu, Mingyue Guo, Lixuan He, Maria-Aranzazu Martinez, Marta Martinez, Bernardo Lopez-Torres, Maria-Rosa Martinez-Larranaga, Xu Wang, Arturo Anadon, Irma Ares
Summary: Deoxynivalenol (DON) is a common contaminant in cereals for infants and can cause growth retardation and inflammation in children. The present research reveals that nicotinamide N-methyltransferase (NNMT) acts as a self-protective factor in DON-exposed cells, alleviating cell growth inhibition by reducing the production of pro-inflammatory cytokines.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Karen H. DeBalsi, John J. Newman, Laura A. Sommerville, John Phillips III, Rizwan Hamid, Joy P. Cogan, Joshua M. Fessel, Anne Evans, Adam Kennedy
Summary: We presented a case study of a 20-year-old male with an unknown neurodegenerative disease, and found that the patient had a dysfunction in nicotinamide N-methyltransferase (NNMT) through metabolic profiling analysis. This study serves as an important reference in the rare disease literature and demonstrates the utility of metabolomics in diagnosing uncharacterized metabolic diseases.
Article
Oncology
Wei Sun, Yongxiang Zou, Zheng Cai, Jinxiang Huang, Xinjie Hong, Qiang Liang, Weilin Jin
Summary: NNMT is found to be overexpressed in glioma and is associated with poor prognosis. Knockdown of NNMT reduces the volume of glioma and the viability of glioma cells. Overexpression of NNMT epigenetically silences GAP43 and inhibits tumor growth and induces apoptosis through the SIRT1 signaling pathway.
Article
Plant Sciences
Enhui Yao, Xiazhen Yang, Xuefeng Huang, Yuchen Mi, Xiaoqian Wu, Meijuan Fang, Jinhua Huang, Yan Qiu, Xiaoting Hong, Lu Peng, Jie Ren, Rui Huang, Caixia Chen, Lichao Yang, Yu Zhou, Rengong Zhuo, Xin Jin, Yun Zhao
Summary: WDL reduces fat mass, suppresses body weight gain, and improves obesity-related metabolic disorders in DIO mice. WDL promotes adipose browning and enhances energy expenditure. WDL reverses obesity through inhibiting NNMT and activating the SIRT1/AMPK/PPAR alpha pathway.
Article
Obstetrics & Gynecology
Zeliha Esin Celik, Serra Akar, Siddika Findik, Emine Aytekin, Cetin Celik
Summary: This study showed that NNMT expression was elevated in vulvar SCC compared to benign and premalignant lesions. Additionally, elevated NNMT expression was associated with poor survival.
JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lucrezia Togni, Marco Mascitti, Davide Sartini, Roberto Campagna, Valentina Pozzi, Eleonora Salvolini, Annamaria Offidani, Andrea Santarelli, Monica Emanuelli
Summary: NNMT is significantly overexpressed in various HNT types and has been associated with cancer cell migration and adverse clinical outcomes. However, its prognostic significance in OSCC remains debated, and further studies on larger patient cohorts are needed to explore its biological role in HNT.
Article
Biochemistry & Molecular Biology
Matthijs J. van Haren, Martin G. Thomas, Davide Sartini, David J. Barlow, David B. Ramsden, Monica Emanuelli, Fabio Klamt, Nathaniel Martin, Richard B. Parsons
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2018)
Article
Medicine, General & Internal
Martin Geoffrey Thomas, Carrie Bayliss, Simon Bond, Francis Dowling, James Galea, Vipul Jairath, Christopher Lamb, Christopher Probert, Elizabeth Timperley-Preece, Alastair Watson, Lynne Whitehead, John G. Williams, Miles Parkes, Arthur Kaser, Tim Raine
Article
Neurosciences
Liana M. de Medeiros, Marco A. De Bastiani, Eduardo P. Rico, Patricia Schonhofen, Bianca Pfaffenseller, Bianca Wollenhaupt-Aguiar, Lucas Grun, Florencia Barbe-Tuana, Eduardo R. Zimmer, Mauro A. A. Castro, Richard B. Parsons, Fabio Klamt
MOLECULAR NEUROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Rakhee J. Mistry, Fabio Klamt, David B. Ramsden, Richard B. Parsons
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2020)
Review
Oncology
Ivi Juliana Bristot, Camila Kehl Dias, Henrique Chapola, Richard B. Parsons, Fabio Klamt
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2020)
Article
Neurosciences
D. M. Vargas, M. A. De Bastiani, R. B. Parsons, F. Klamt
Summary: Parkinson's disease is a complex neurodegenerative disease influenced by both genetic and environmental factors. By reconstructing transcriptional regulatory networks of affected brain regions, potential therapeutic interventions have been identified through master regulator candidates. Using computational drug repositioning, new drugs have been suggested as potential therapies for Parkinson's disease.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Neurosciences
Altin Kocinaj, Tabassum Chaudhury, Mohammed S. Uddin, Rashad R. Junaid, David B. Ramsden, Geshanthi Hondhamuni, Fabio Klamt, Linda Parsons, Richard B. Parsons
Summary: The study demonstrates that NNMT protein expression is increased in the AD brain, mainly in cholinergic neurones, suggesting it may be a common feature in numerous neurodegenerative diseases. Confirming this overexpression in a larger AD patient cohort could lead to the development of NNMT-targeted therapeutics to slow or halt disease progression, in contrast to current symptomatic treatments for AD.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemical Research Methods
Amita Puranik, Marianne Saldanha, Prajakta Dandekar, Ratnesh Jain
Summary: This study compared four commonly used techniques for estimating protein molecular weight and found that glycosylation has the least impact on SEC-MALS and SV-AUC, but significantly affects LC-MS and SDS-PAGE. Therefore, the structural characteristics of proteins should be considered when selecting an appropriate technique for determining their molecular weight.
Article
Biochemistry & Molecular Biology
Richard B. Parsons, Altin Kocinaj, Gustavo Ruiz Pulido, Sarah A. Prendergast, Anna E. Parsons, Paul D. Facey, Frank Hirth
Summary: Parkinson's disease is characterized by alpha-synuclein deposition, which results in synaptic dysfunction and progressive neurodegeneration. This study found significantly decreased levels of NMNAT3 protein in the caudate nucleus of Parkinson's disease patients, which correlated with the amount of alpha-synuclein. The findings suggest that alterations in the NAD+ biosynthetic pathway are implicated in alpha-synuclein-mediated synaptopathy.
HUMAN MOLECULAR GENETICS
(2022)
Review
Biotechnology & Applied Microbiology
Amita Puranik, Marianne Saldanha, Narendra Chirmule, Prajakta Dandekar, Ratnesh Jain
Summary: Glycosylation plays a crucial role in defining the safety and efficacy of biopharmaceuticals, but controlling glycan heterogeneity has always been challenging. Traditional approaches and emerging technologies are being utilized for controlling and predicting glycosylation, paving the way for automated bioprocesses.
BIOTECHNOLOGY PROGRESS
(2022)
Article
Biotechnology & Applied Microbiology
Marianne Saldanha, Ashutosh Shelar, Vaibhav Patil, Vishal G. Warke, Prajakta Dandekar, Ratnesh Jain
Summary: This case-study demonstrates an approach for identifying correlations between nutrients/metabolites in CHO cell cultures and cell growth, mAb titre, and critical quality attributes using multivariate analyses. The study uses an extensive LC-MS-based method to analyze the spent medium composition and employs PLS and OPLS models to determine the correlations between nutrient composition and cell growth/mAb titre, as well as the effect of changing nutrient composition on critical quality attributes. The results reveal the importance of certain amino acids, vitamins, and intermediates in the culture process and provide opportunities for optimizing growth media and feed media for better cell growth, mAb production, and quality.
Article
Biotechnology & Applied Microbiology
Marianne Saldanha, Krutika Padhye, Vishal G. Warke, Prajakta Dandekar, Ratnesh Jain
Summary: In this study, a simple strategy of enriching existing feed with TCA cycle intermediates and precursors was demonstrated to effectively increase mAb production by > 50% without affecting quality attributes. The individually tested TCA compounds and mixtures showed that succinate supplementation resulted in superior cell growth and significant reduction in ammonia production.
BIOCHEMICAL ENGINEERING JOURNAL
(2023)
Article
Biochemical Research Methods
Shashikant Doltade, Marianne Saldanha, Vaibhav Patil, Prajakta Dandekar, Ratnesh Jain
Summary: This study investigated the impact of various process parameters on the concentration and quality of monoclonal antibodies purified by Protein A chromatography. Critical parameters were identified and optimized using experimental design. The elution pH primarily affected the concentration and content of monomers and aggregates, while the Tween concentration mainly influenced the main peak of charge variants. This study highlights the importance of considering multiple parameters in protein A purification for achieving desired product quality.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2023)
Article
Chemistry, Analytical
Prity Kumari, Marianne Saldanha, Ratnesh Jain, Prajakta Dandekar
Summary: Addition of sugar osmolytes and formulation excipients can effectively reduce monoclonal antibody aggregation during cell culture, improving downstream processing and process yield.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Review
Neurosciences
David B. Ramsden, Rosemary H. Waring, Richard B. Parsons, David J. Barlow, Adrian C. Williams
INTERNATIONAL JOURNAL OF TRYPTOPHAN RESEARCH
(2020)