02643nas a2200301 4500008004100000022001400041245005500055210005500110260006700165300001200232490000700244520171800251653001701969653001201986653001401998653001102012653002002023653000902043100002502052700002302077700002102100700002402121700002102145700003602166700002802202700002502230856008602255 2015 eng d a1615-985300aInvestigation of phosphoproteome in RAGE signaling0 aInvestigation of phosphoproteome in RAGE signaling a111 RIVER ST, HOBOKEN 07030-5774, NJ USAbWILEY-BLACKWELLcJAN a245-2590 v153 a

The receptor for advanced glycation end products (RAGE) is one of the most important proteins implicated in diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer. It is a pattern recognition receptor by virtue of its ability to interact with multiple ligands, RAGE activates several signal transduction pathways through involvement of various kinases that phosphorylate their respective substrates. Only few substrates have been known to be phosphorylated in response to activation by RAGE (e.g., nuclear factor kappa B); however, it is possible that these kinases can phosphorylate multiple substrates depending upon their expression and localization, leading to altered cellular responses in different cell types and conditions. One such example is, glycogen synthase kinase 3 beta which is known to phosphorylate glycogen synthase, acts downstream to RAGE, and hyperphosphorylates microtubule-associated protein tau causing neuronal damage. Thus, it is important to understand the role of various RAGE-activated kinases and their substrates. Therefore, we have reviewed here the details of RAGE-activated kinases in response to different ligands and their respective phosphoproteome. Furthermore, we discuss the analysis of the data mined for known substrates of these kinases from the PhosphoSitePlus (http://www.phosphosite.org) database, and the role of some of the important substrates involved in cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. In summary, this review provides information on RAGE-activated kinases and their phosphoproteome, which will be helpful in understanding the possible role of RAGE and its ligands in progression of diseases.

10aCell biology10aDisease10aGlycation10aKinase10aPhosphoproteome10aRAGE1 aBatkulwar, Kedar, B.1 aBansode, Sneha, B.1 aPatil, Gouri, V.1 aGodbole, Rashmi, K.1 aKazi, Rubina, S.1 aChinnathambi, Subashchandrabose1 aShanmugam, Dhanasekaran1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/investigation-phosphoproteome-rage-signaling-002674nas a2200229 4500008004100000245012800041210006900169260000800238300000800246490000700254520187200261653002402133653002002157653001602177653001402193653001102207653000802218100003402226700001602260700003602276856013202312 2020 eng d00aInteraction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferation0 aInteraction of Tau with the chemokine receptor CX3CR1 and its ef cSEP a1090 v103 a

Alzheimer's disease (AD) is a neurodegenerative disease that leads to progressive loss of memory and dementia. The pathological hallmarks of AD include extracellular accumulation of amyloid-beta peptides forming senile plaques and intracellular accumulation of Tau oligomers and filamentous species. Tau is a microtubule-binding protein that stabilizes tubulin to form microtubules under physiological condition. In AD/ pathological condition, Tau detaches from microtubules and aggregates to form oligomers of different sizes and filamentous species such as paired helical filaments. Microglia are the resident brain macrophages that are involved in the phagocytosis of microbes, cellular debris, misfolded and aggregated proteins. Chemokine receptor, CX3CR1 is mostly expressed on microglia and is involved in maintaining the microglia in a quiescent state by binding to its ligand, fractalkine (CX3CL1), which is expressed in neurons as both soluble or membrane-bound state. Hence, under physiological conditions, the CX3CR1/CX3CL1 axis plays a significant role in maintaining the central nervous system (CNS) homeostasis. Further, CX3CR1/CX3CL1 signalling is involved in the synthesis of anti-inflammatory cytokines and also has a significant role in cytoskeletal rearrangement, migration, apoptosis and proliferation. In AD brain, the expression level of fractalkine is reduced, and hence Tau competes to interact with its receptor, CX3CR1. In microglia, phagocytosis and internalization of extracellular Tau species occurs in the presence of a chemokine receptor, CX3CR1 which binds directly to Tau and promotes its internalization. In this review, the pathophysiological roles of CX3CR1/fractalkine signalling in microglia and neurons at different stages of Alzheimer's disease and the possible role of CX3CR1/Tau signalling has been widely discussed.

10aAlzheimer's disease10aCX3CR1 receptor10aFractalkine10amicroglia10aNeuron10aTau1 aChidambaram, Hariharakrishnan1 aDas, Rashmi1 aChinnathambi, Subashchandrabose uhttps://library.ncl.res.in/content/interaction-tau-chemokine-receptor-cx3cr1-and-its-effect-microglial-activation-migration-and02109nas a2200217 4500008004100000022001400041245009700055210006900152260000800221300001200229490000800241520134500249653001401594653001401608653001901622653003201641653003101673100003601704700002801740856012301768 2021 eng d a0306-452200aImplications of valosin-containing protein in promoting autophagy to prevent tau aggregation0 aImplications of valosincontaining protein in promoting autophagy cNOV a125-1340 v4763 aand cellular degradative mechanisms modulate Tau aggregation. During aging and neu-rodegenerative disorders, the cellular proteostasis is disturbed due to impaired protective mechanisms. This results in accumulation of aberrant Tau aggregates in the neuron that leads to microtubule destabilization and neuronal degeneration. The intricate mechanisms to prevent Tau aggregation involve chaperones, autophagy, and proteasomal system have gained main focus about concerning to therapeutic intervention. However, the thor-ough understanding of other key proteins, such as Valosin-containing protein (VCP), is limited. In various neu-rodegenerative diseases, the chaperone-like activity of VCP is involved in preventing protein aggregation and mediating the degradation of aberrant proteins by proteasome and autophagy. In the case of Tau aggregation associated with Alzheimer's disease, the importance of VCP is poorly understood. VCP is known to co-localize with Tau, and alterations in VCP cause aberrant accumulation of Tau. Nevertheless, the direct mechanism of VCP in altering Tau aggregation is not known. Hence, we speculate that VCP might be one of the key modulators in preventing Tau aggregation and can disintegrate Tau aggregates by directing its clearance by autophagy. = 2021 IBRO. Published by Elsevier Ltd. All rights reserved.10aAutophagy10asegregase10aTau aggregates10aUbiquitin-proteasome system10avalosin-containing protein1 aChinnathambi, Subashchandrabose1 aGorantla, Nalini, Vijay uhttps://library.ncl.res.in/content/implications-valosin-containing-protein-promoting-autophagy-prevent-tau-aggregation02537nas 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

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.

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-vitro02225nas 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

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.

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