02515nas a2200217   4500008004100000022001400041245008600055210006900141260000800210300000900218490000700227520175600234100002801990700001602018700003402034700001802068700002202086700003302108700003602141856012002177       2020                        eng d  a2045-232200aBasic limonoid modulates chaperone-mediated proteostasis and dissolve Tau fibrils0 aBasic limonoid modulates chaperonemediated proteostasis and diss  cMAR  a40230 v103 a<p>The Alzheimer's disease pathology is associated with accumulation of intracellular neurofibrillary tangles and extracellular senile plaques. The formation of initial nucleus triggers conformational changes in Tau and leads to its deposition. Hence, there is a need to eliminate these toxic proteins for proper functioning of neuronal cells. In this aspect, we screened the effect of basic limonoids such as gedunin, epoxyazadiradione, azadirone and azadiradione on inhibiting Tau aggregation as well as disintegration of induced Tau aggregates. It was observed that these basic limonoids effectively prevented aggregates formation by Tau and also exhibited the property of destabilizing matured Tau aggregates. The molecular docking analysis suggests that the basic limonoids interact with hexapeptide regions of aggregated Tau. Although these limonoids caused the conformational changes in Tau to beta-sheet structure, the cytological studies indicate that basic limonoids rescued cell death. The dual role of limonoids in Tau aggregation inhibition and disintegration of matured aggregates suggests them to be potent molecules in overcoming Tau pathology. Further, their origin from a medicinally important plant neem, which known to possess remarkable biological activities was also found to play protective role in HEK293T cells. Basic limonoids were non-toxic to HEK293T cells and also aided in activation of HSF1 by inducing its accumulation in nucleus. Western blotting and immunofluorescence studies showed that HSF1 in downstream increased the transcription of Hsp70 thus, aggravating cytosolic Hsp70 levels that can channel clearance of aberrant Tau. All these results mark basic limonoids as potential therapeutic natural products.</p>
1 aGorantla, Nalini, Vijay1 aDas, Rashmi1 aChidambaram, Hariharakrishnan1 aDubey, Tushar1 aMulani, Fayaj, A.1 aThulasiram, Hirekodathakallu1 aChinnathambi, Subashchandrabose  uhttp://library.ncl.res.in/content/basic-limonoid-modulates-chaperone-mediated-proteostasis-and-dissolve-tau-fibrils02559nas a2200313   4500008004100000022001400041245010100055210006900156260000800225300001100233490000800244520153800252653002601790653001201816653001201828653003301840653001401873653002801887653001701915653002901932653002001961100002001981700002502001700001902026700001802045700003302063700002002096856012902116       2020                        eng d  a0031-942200aBiosynthesis and tissue-specific partitioning of camphor and eugenol in Ocimum kilimandscharicum0 aBiosynthesis and tissuespecific partitioning of camphor and euge  cSEP  a1124510 v1773 a<p>In Ocimum kilimandscharicum, the relative volatile composition of camphor in leaves was as high as 55%, while that of eugenol in roots was 57%. These metabolites were differentially partitioned between the aerial and root tissues. Global metabolomics revealed tissue-specific biochemical specialization, evident by the differential distribution of 2588 putative metabolites across nine tissues. Next-generation sequencing analysis indicated differential expression of 51 phenylpropanoid and 55 terpenoid pathway genes in aerial and root tissues. By integrating metabolomics with transcriptomics, the camphor biosynthesis pathway in O. kilimandscharicum was elucidated. In planta bioassays revealed the role of geranyl diphosphate synthase (gpps) and borneol dehydrogenase (bdh) in camphor biosynthesis. Further, the partitioning of camphor was attributed to tissue-specific gene expression of both the pathway entry point (gpps) and terminal (bdh) enzyme. Unlike camphor, eugenol accumulated more in roots; however, absence of the eugenol synthase gene in roots indicated long distance transport from aerial tissues. In silico co-expression analysis indicated the potential involvement of ATP-binding cassette, multidrug and toxic compound extrusion, and sugar transporters in eugenol transport. Similar partitioning was evident across five other Ocimum species. Overall, our work indicates that metabolite partitioning maybe a finely regulated process, which may have implications on plant growth, development, and defense.</p>
10aBorneol dehydrogenase10aCamphor10aEugenol10aGeranyl diphosphate synthase10aLamiaceae10aMetabolite partitioning10aMetabolomics10aOcimum kilimandscharicum10aTranscriptomics1 aSingh, Priyanka1 aKalunke, Raviraj, M.1 aShukla, Anurag1 aTzfadia, Oren1 aThulasiram, Hirekodathakallu1 aGiri, Ashok, P.  uhttp://library.ncl.res.in/content/biosynthesis-and-tissue-specific-partitioning-camphor-and-eugenol-ocimum-kilimandscharicum