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  • Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Application


    Nicotinamide mononucleotide (NMN) is a nucleotide that is most recognized for its role as an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis. Although the biosynthetic pathway of NMN varies between eukaryote and prokaryote, two pathways are mainly followed in case of eukaryotic human—one is through the salvage pathway using nicotinamide while the other follows phosphorylation of nicotinamide riboside. Due to the unavailability of a suitable transporter, NMN enters inside the mammalian cell in the form of nicotinamide riboside followed by its subsequent conversion to NMN and NAD+. This particular molecule has demonstrated several beneficial pharmacological activities in preclinical studies, which suggest its potential therapeutic use.

    【 MORE 】 Time: 2019-07-11
  • NAD metabolic dependency in cancer is shaped by gene amplification and enha


    Precision oncology hinges on linking tumour genotype with molecularly targeted drugs; however, targeting the frequently dysregulated metabolic landscape of cancer has proven to be a major challenge. Here we show that tissue context is the major determinant of dependence on the nicotinamide adenine dinucleotide (NAD) metabolic pathway in cancer. By analysing more than 7,000 tumours and 2,600 matched normal samples of 19 tissue types, coupled with mathematical modelling and extensive in vitro and in vivo analyses, we identify a simple and actionable set of ‘rules’. If the rate-limiting enzyme of de novo NAD synthesis, NAPRT, is highly expressed in a normal tissue type, cancers that arise from that tissue will have a high frequency of NAPRT amplification and be completely and irreversibly dependent on NAPRT for survival. By contrast, tumours that arise from normal tissues that do not express NAPRT highly are entirely dependent on the NAD salvage pathway for survival. We identify the previously unknown enhancer that underlies this dependence. 

    【 MORE 】 Time: 2019-07-11
  • UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis


    Cancer metastasis is the primary cause of morbidity and mortality, and accounts for up to 95% of cancer-related deaths¹. Cancer cells often reprogram their metabolism to efficiently support cell proliferation and survival2,3. However, whether and how those metabolic alterations contribute to the migration of tumour cells remain largely unknown. UDP-glucose 6-dehydrogenase (UGDH) is a key enzyme in the uronic acid pathway, and converts UDP-glucose to UDP-glucuronic acid⁴. 

    【 MORE 】 Time: 2019-07-11
  • Anti-Aging Researcher David Sinclair Takes Metformin, NMN, NAD for Longevit


    Sinclair’s lab continues to work on resveratrol and analogs of it, as well as on mitochondria and NAD, all directed to understanding aging and how to prevent it.

    His antiaging regimen is to activate pathways to improve the bodies defenses against aging.He is testing NMN on human subjects. He describes NMN is fuel for sirtuins. NMN is related to NR. NR increases the levels of NAD. Sirtuins need NAD to work. We lose NAD as we age. We have half of the NAD by the time we are 50.

    【 MORE 】 Time: 2019-07-10
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