02516nas a2200217   4500008004100000022001400041245008600055210006900141260000800210300000900218490000700227520175600234100002801990700001602018700003402034700001802068700002202086700003302108700003602141856012102177       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  uhttps://library.ncl.res.in/content/basic-limonoid-modulates-chaperone-mediated-proteostasis-and-dissolve-tau-fibrils02240nas a2200277   4500008004100000022001400041245007900055210006900134260000800203300001100211490000800222520137500230653002001605653001501625653000901640653002201649653001101671653002001682653002401702100001801726700002101744700002301765700002701788700003601815856011101851       2023                        eng d  a0141-813000aBacopa monnieri reduces Tau aggregation and Tau-mediated toxicity in cells0 aBacopa monnieri reduces Tau aggregation and Taumediated toxicity  cAPR  a1231710 v2343 a<p>
	Alzheimer's disease is a neurodegenerative disease characterized by progressive memory loss and behavioral impairments. In the present study, the ethanolic extract of Bacopa monnieri was studied for its potency to inhibit Tau aggregation and rescuing of the viability of Tau-stressed cells. Bacopa monnieri was observed to inhibit the Tau aggregation in vitro. The cells exposed to Bacopa monnieri were also observed to have a low level of ROS and caspase-3 activity. The immunoblot and immunofluorescence analysis showed that Bacopa monnieri acts as an antioxidant and restored the Nrf2 levels in Neuro2a cells. Bacopa monnieri treatment to Neuro2a cells was observed to reduce the phospho-Tau load in formaldehyde-stressed cells. Furthermore, the treatment of Bacopa monnieri reduced the phosphorylation of GSK-3 beta in formaldehyde-stressed cells. Ran and NUP358 are the key proteins involved in nuclear transport. It was observed that formaldehyde treatment impaired the nuclear transport by missorting the NUP358 arrangement in Neuro2a cells. On the contrary, Bacopa monnieri treatment restored the NUP358 arrangement in cells. The overall results of the present study suggested that Bacopa monnieri could be considered a potent herb against Tau phosphorylation and Tau aggregation, which projects it as a promising formulation for Alzheimer's disease.</p>
10aBacopa monnieri10aGSK-3 beta10aNrf210aNuclear transport10aNUP35810aTau Aggregation10aTau phosphorylation1 aDubey, Tushar1 aKushwaha, Preeti1 aThulasiram, H., V.1 aChandrashekar, Madhura1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/bacopa-monnieri-reduces-tau-aggregation-and-tau-mediated-toxicity-cells