02655nas a2200181   4500008004100000022001400041245008000055210006900135260000900204300001600213490000600229520200500235100001802240700002802258700004002286700003602326856011102362       2019                        eng d  a2470-134300aPhotoexcited toluidine blue inhibits tau aggregation in Alzheimer's disease0 aPhotoexcited toluidine blue inhibits tau aggregation in Alzheime  cNOV   a18793-188020 v43 a<p>The aggregates of microtubule-associated protein Tau are considered as a major hallmark of Alzheimer's disease. Tau aggregates accumulate intracellularly leading to neuronal toxicity. Numerous approaches have been targeted against Tau protein aggregation, which include application of synthetic and natural compounds. Toluidine blue is a basic dye of phenothiazine family, which on irradiation with a 630 nm light gets converted into a photoexcited form, leading to generation of singlet oxygen species. Methylene blue is the parent compound of toluidine blue, which has been reported to be potent against tauopathy. In the present work, we studied the potency of toluidine blue and photoexcited toluidine blue against Tau aggregation. Biochemical and biophysical analyses using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, ThS fluorescence, circular dichroism spectroscopy, and electron microscopy suggested that toluidine blue inhibited the aggregation of Tau in vitro. The photoexcited toluidine blue potentially dissolved the matured Tau fibrils, which indicated the disaggregation property of toluidine blue. The cell biology studies including the cytotoxicity assay and reactive oxygen species (ROS) production assay suggested toluidine blue to be a biocompatible dye as it reduced ROS levels and cell death. The photoexcited toluidine blue modulates the cytoskeleton network in cells, which was supported by immunofluorescence studies of neuronal cells. The studies in a UAS Tau E14 transgenic Drosophila model suggested that photoexcited toluidine blue was potent to restore the survival and memory deficits of Drosophila. The overall finding of our studies suggested toluidine blue to be a potent molecule in rescuing the Tau-mediated pathology by inhibiting its aggregation, reducing the cell death, and modulating the tubulin levels and behavioral characteristics of Drosophila. Thus, toluidine blue can be addressed as a potent molecule against Alzheimer's disease.</p>
1 aDubey, Tushar1 aNalini, Gorantla, Vijay1 aChandrashekara, Kagepura, Thammaiah1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/photoexcited-toluidine-blue-inhibits-tau-aggregation-alzheimers-disease02516nas 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-fibrils02326nas a2200181   4500008004100000022001400041245011900055210006900174260000800243300001000251490000700261520162900268100001801897700002801915700004001943700003601983856012502019       2020                        eng d  a2045-232200aPhotodynamic exposure of Rose-Bengal inhibits Tau aggregation and modulates cytoskeletal network in neuronal cells0 aPhotodynamic exposure of RoseBengal inhibits Tau aggregation and  cJUL  a123800 v103 a<p>The intracellular Tau aggregates are known to be associated with Alzheimer's disease. The inhibition of Tau aggregation is an important strategy for screening of therapeutic molecules in Alzheimer's disease. Several classes of dyes possess a unique property of photo-excitation, which is applied as a therapeutic measure against numerous neurological dysfunctions. Rose Bengal is a Xanthene dye, which has been widely used as a photosensitizer in photodynamic therapy. The aim of this work was to study the protective role of Rose Bengal against Tau aggregation and cytoskeleton modulations. The aggregation inhibition and disaggregation potency of Rose Bengal and photo-excited Rose Bengal were observed by in-vitro fluorescence, circular dichroism, and electron microscopy. Rose Bengal and photo-excited Rose Bengal induce minimal cytotoxicity in neuronal cells. In our studies, we observed that Rose Bengal and photo-excited Rose Bengal modulate the cytoskeleton network of actin and tubulin. The immunofluorescence studies showed the increased filopodia structures after photo-excited Rose Bengal treatment. Furthermore, Rose Bengal treatment increases the connections between the cells. Rose Bengal and photo-excited Rose Bengal treatment-induced actin-rich podosome-like structures associated with cell membranes. The in-vivo studies on UAS E-14 Tau mutant Drosophila suggested that exposure to Rose Bengal and photo-excited Rose Bengal efficiency rescues the behavioural and memory deficit in flies. Thus, the overall results suggest that Rose Bengal could have a therapeutic potency against Tau aggregation.</p>
1 aDubey, Tushar1 aGorantla, Nalini, Vijay1 aChandrashekara, Kagepura, Thammaiah1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/photodynamic-exposure-rose-bengal-inhibits-tau-aggregation-and-modulates-cytoskeletal02078nas a2200229   4500008004100000022001400041245008100055210006900136260000900205300001200214490000800226520130500234653002501539653002401564653002001588653002101608653002301629100002601652700001801678700003601696856011601732       2021                        eng d  a0141-813000aAlpha-Linolenic acid inhibits Tau aggregation and modulates Tau conformation0 aAlphaLinolenic acid inhibits Tau aggregation and modulates Tau c  cJAN   a687-6930 v1663 a<p>Alzheimer's disease is characterized by important patho-proteins, which being composed of Amyloid-beta, plaques and intracellular neurofibrillary tangles of Tau. Intrinsically disordered protein tau has several interacting partners, which are necessary for its normal functioning. Tau has been shown to interact with various proteins, nucleic acid, and lipids. alpha-Linolenic acid (ALA) a plant-based omega-3 fatty acid has been studied for its role as neuroprotective and beneficial fatty add in the brain. In this study, we are focusing on the ability of ALA to induce spontaneous assembly in tau protein. ALA inhibited the Tau aggregation as indicated by reduced ThS fluorescence kinetics, which indicates no aggregation of Tau. Similarly, SDS-PAGE analysis supported that ALA exposure inhibited the aggregation as no higher-order tau species were observed. Along with its ability to impede the aggregation of Tau, ALA also maintains a native random coiled structure, which was estimated by CD spectroscopy. Finally, TEM analysis showed that the formation of Tau fibrils was found to be discouraged by ALA. Hence, conclusion of the study suggested that ALA profoundly inhibited aggregation of Tau and maintained it's the random-coil structure. (C) 2020 Elsevier B.V. All rights reserved.</p>
10aalpha-linolenic acid10aAlzheimer's disease10aFree fatty adds10aTau conformation10aTau fibrillization1 aDesale, Smita, Eknath1 aDubey, Tushar1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/alpha-linolenic-acid-inhibits-tau-aggregation-and-modulates-tau-conformation02537nas a2200193   4500008004100000245019700041210006900238260000800307300001200315490000800327520173600335100002502071700001502096700001802111700003602129700002802165700001902193856013102212       2021                        eng d00aInfluence of sodium caseinate, maltodextrin, pectin and their Maillard conjugate on the stability, in vitro release, anti-oxidant property and cell viability of eugenol-olive oil nanoemulsions0 aInfluence of sodium caseinate maltodextrin pectin and their Mail  cJUL  a158-1700 v1833 a<p><span style="color: rgb(33, 33, 33); font-family: BlinkMacSystemFont, -apple-system, &quot;Segoe UI&quot;, Roboto, Oxygen, Ubuntu, Cantarell, &quot;Fira Sans&quot;, &quot;Droid Sans&quot;, &quot;Helvetica Neue&quot;, sans-serif; font-size: 16px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">The influence of protein (sodium caseinate-SC), polysaccharide (maltodextrin-MD; pectin-PC) and their Maillard conjugates (sodium caseinate maltodextrin conjugate-SCMDC; sodium caseinate pectin conjugate-SCPCC) were studied on the physico-chemical and biological properties of eugenol nanoemulsions/powder. The chemical composition was optimized using Taguchi design. The particles size of eugenol nanoemulsions with SC, MD, PC, SCMDC and SCPCC were 104.6, 323.5, 1872, 181.7, and 454.4 nm, respectively while their zeta potentials were -31.2, -28.5, -21.4, -40.1 and -25.1 mV, respectively. Turbidity studies revealed higher stability of nanoemulsion prepared with Maillard conjugate (SCMDC) compared to protein or polysaccharides alone. The dispersion of SCMDC eugenol nanoparticles in buffer was prepared to study its stability at different pH (3.0, 5.0, and 7.0) and temperature (4°, 37°, 60 °C) range. In-vitro enzymatic release study showed 31 and 74% release of eugenol after 6 h at pH 2.4 and 7.4, respectively. In vitro antioxidant capacity of SCMDC encapsulated eugenol was higher than native eugenol, as demonstrated by free radical scavenging assays. In comparison to native eugenol, E:SCMDC eugenol showed reduced toxicity. These findings suggested that nanoencapsulated eugenol (E:SCMDC) have a huge potential in nutraceutical and therapeutic applications.</span></p>1 aNagaraju, Pramod, G.1 aSindhu, P.1 aDubey, Tushar1 aChinnathambi, Subashchandrabose1 aPriyadarshini, Poornima1 aRao, Pooja, J.  uhttps://library.ncl.res.in/content/influence-sodium-caseinate-maltodextrin-pectin-and-their-maillard-conjugate-stability-vitro01857nas a2200241   4500008004100000022001400041245008900055210006900144260000800213300001200221490000700233520106600240653001001306653001901316653002801335653002601363653002501389653001401414653001201428100001801440700003601458856012101494       2021                        eng d  a1949-358400aPhotodynamic sensitizers modulate cytoskeleton structural dynamics in neuronal cells0 aPhotodynamic sensitizers modulate cytoskeleton structural dynami  cJUN  a232-2480 v783 a<p>The neuronal cytoskeleton plays a crucial role in maintaining cell integrity and functioning of neurons. Cytoskeleton deformities have been reported to be associated with neurodegenerative diseases thus; cytoskeleton can be targeted for therapeutic strategies. The therapeutic application of photosensitive molecule is termed as photodynamic therapy (PDT). PDT has been applied in the field of dermatology, cancer biology, and antimicrobial therapy. PDT induces several changes in cells, which include induction of apoptosis, DNA damage, and induction of inflammatory response. PDT has been also reported to modulate cytoskeleton such as actin dynamics. The in vitro studies suggested that PDT using dyes such as Toluidine Blue and Rose Bengal effectively modulated the actin cytoskeleton, neurite outgrowth, tubulin, and Tau aggregation. In this review, we focused on the effect of photosensitized molecules on various cytoskeleton proteins. We hypothesize that PDT could have potency against Alzheimer's disease and other neurodegenerative disorders.</p>
10aActin10aAlzheimer&apos10acytoskeleton modulation10aneuronal cytoskeleton10aphotodynamic therapy10as disease10aTubulin1 aDubey, Tushar1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/photodynamic-sensitizers-modulate-cytoskeleton-structural-dynamics-neuronal-cells01544nas a2200133   4500008004100000245009800041210006900139260000800208300000900216520100100225100001801226700003601244856013001280       2021                        eng d00aPhotodynamic treatment modulates various GTPase and cellular signalling pathways in Tauopathy0 aPhotodynamic treatment modulates various GTPase and cellular sig  cJUN  a1-133 aABSTRACTThe application of photo-excited dyes for treatment is known as photodynamic therapy (PDT). PDT is known to target GTPase proteins in cells, which are the key proteins of diverse signalling cascades which ultimately modulate cell proliferation and death. Cytoskeletal proteins play critical roles in maintaining cell integrity and cell division. Whereas, it was also observed that in neuronal cells PDT modulated actin and tubulin resulting in increased neurite growth and filopodia. Recent studies supported the role of PDT in dissolving the extracellular amyloid beta aggregates and intracellular Tau aggregates, which indicated the potential role of PDT in neurodegeneration. The advancement in the field of PDT led to its clinical approval in treatment of cancers, brain tumour, and dermatological acne. Although several question need to be answered for application of PDT in neuronal cells, but the primary studies gave a hint that it can emerge as potential therapy in neural cells.1 aDubey, Tushar1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/photodynamic-treatment-modulates-various-gtpase-and-cellular-signalling-pathways-tauopathy02240nas 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-cells02225nas a2200241   4500008004100000022001400041245010200055210006900157260000800226490000800234520137900242653001601621653001301637653002001650653002001670100001801690700002901708700002801737700002401765700002701789700003601816856013101852       2023                        eng d  a0927-776500aInhibitory effect of curcumin-artemisinin co-amorphous on Tau aggregation and Tau phosphorylation0 aInhibitory effect of curcuminartemisinin coamorphous on Tau aggr  cJAN0 v2213 a<p>
	Tau is a natively unfolded microtubule-associated protein. Tau neurofibrillary tangles are one of the hallmarks of Alzheimer's disease. The post-translational modifications of Tau lead to its pathological state. Phosphorylation is the key post-translational modification associated with Tauopathy. Curcumin is a polyphenolic compound pre-sent in the rhizomes of Curcuma longa. Curcumin has been reported to have remarkable medicinal properties in several diseases, but its poor solubility limits its therapeutic potency. Artemisinin is a sesquiterpene lactone, which has been known sience ancient times for its applications as a treatment for various diseases such as malaria, cancer, autoimmune disease, etc. In the present study, the potency of crystalline curcumin, crystalline artemisinin, and Cur-Art co-amorphous dispersion were evaluated against Tau pathology. The in-vitro ThS/ANS fluorescence and electron microscopy results suggested that curcumin and Cur-Art efficiently inhibited Tau aggregation. Furthermore, exposure to curcumin and Cur-Art co-amorphous restored the impaired nuclear transport in formaldehyde-stressed cells. Curcumin was also found to modulate the phosphorylation of Tau, which indicated the neuroprotective potency. Thus, curcumin and Cur-Art co-amorphous exhibit therapeutic potential against Tau protein in Alzheimer's disease.</p>
10aartemisinin10acurcumin10aPhosphorylation10aTau Aggregation1 aDubey, Tushar1 aSonawane, Shweta, Kishor1 aMannava, M., K. Chaitan1 aNangia, Ashwini, K.1 aChandrashekar, Madhura1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/inhibitory-effect-curcumin-artemisinin-co-amorphous-tau-aggregation-and-tau-phosphorylation