02024nas a2200193   4500008004100000022001400041245003600055210003600091260000800127300001100135490000700146520151300153653001801666653001801684653002401702100001801726700001901744856006701763       2021                        eng d  a1478-396700aBoolean model for melanogenesis0 aBoolean model for melanogenesis  cMAR  a0260040 v183 a<p>Melanogenesis is a highly regulated process through which the pigment melanin is produced in skin cells. Irregularities in the molecular events that govern the process of skin pigmentation can cause disorders like vitiligo. In order to understand the biology of disease progression, it is important to have an in depth understanding of intracellular events. Mathematical models provide an integrated view of intracellular signalling. There are very few models to date that incorporate intracellular processes relevant to melanogenesis and only one to our knowledge that simulates the dynamics of response to varying levels of input. Here, we report the formulation of the largest Boolean model (265 nodes) for melanogenesis to date. The model was built on the basis of a detailed interaction network graph published by Raghunath et al. Through additional manual curation of the reported interactions, we converted the graph into a set of Boolean rules, following the procedure of the first Boolean model (62 nodes) for melanogenesis published by Lee et al. Simulations show that the predicted response to varying UV levels for most of the nodes is similar to the predictions of the existing model. The greater complexity allows investigation of the sensitivity of melanin to additional nodes. We carried out perturbation analysis of the network through node deletion and constitutive activation to identify sensitivity of outcomes, and compared the nodes identified as sensitive to previous reports.</p>
10aBoolean model10amelanogenesis10aSignal transduction1 aDnyane, Pooja1 aGadgil, Chetan  uhttps://library.ncl.res.in/content/boolean-model-melanogenesis02449nas a2200325   4500008004100000022001400041245010200055210006900157260000800226300001300234490000700247520140400254100001901658700001801677700001801695700002001713700002301733700002001756700001801776700001801794700001801812700002601830700001901856700001901875700002701894700002201921700002501943700002401968856013101992       2022                        eng d  a1544-917300aTemporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator0 aTemporal analysis of melanogenesis identifies fatty acid metabol  cMAY  ae30016340 v203 a<p>
	Therapeutic methods to modulate skin pigmentation has important implications for skin cancer prevention and for treating cutaneous hyperpigmentary conditions. Towards defining new potential targets, we followed temporal dynamics of melanogenesis using a cell-autonomous pigmentation model. Our study elucidates 3 dominant phases of synchronized metabolic and transcriptional reprogramming. The melanogenic trigger is associated with high MITF levels along with rapid uptake of glucose. The transition to pigmented state is accompanied by increased glucose channelisation to anabolic pathways that support melanosome biogenesis. SREBF1-mediated up-regulation of fatty acid synthesis results in a transient accumulation of lipid droplets and enhancement of fatty acids oxidation through mitochondrial respiration. While this heightened bioenergetic activity is important to sustain melanogenesis, it impairs mitochondria lately, shifting the metabolism towards glycolysis. This recovery phase is accompanied by activation of the NRF2 detoxication pathway. Finally, we show that inhibitors of lipid metabolism can resolve hyperpigmentary conditions in a guinea pig UV-tanning model. Our study reveals rewiring of the metabolic circuit during melanogenesis, and fatty acid metabolism as a potential therapeutic target in a variety of cutaneous diseases manifesting hyperpigmentary phenotype.</p>
1 aSultan, Farina1 aBasu, Reelina1 aMurthy, Divya1 aKochar, Manisha1 aAttri, Kuldeep, S.1 aAggarwal, Ayush1 aKumari, Pooja1 aDnyane, Pooja1 aTanwar, Jyoti1 aMotiani, Rajender, K.1 aSingh, Archana1 aGadgil, Chetan1 aBhavesh, Neel, Sarovar1 aSingh, Pankaj, K.1 aNatarajan, Vivek, T.1 aGokhale, Rajesh, S.  uhttps://library.ncl.res.in/content/temporal-analysis-melanogenesis-identifies-fatty-acid-metabolism-key-skin-pigment-regulator