02269nas a2200217 4500008004100000022001400041245010100055210006900156260000800225300001200233490000700245520150100252653002201753653004401775653002301819653000801842653001601850100002901866700003601895856012001931 2018 eng d a0895-869600aPrion-like propagation of post-translationally modified tau in alzheimer's disease: a hypothesis0 aPrionlike propagation of posttranslationally modified tau in alz cAUG a480-4900 v653 a

The microtubule-associated protein Tau plays a key role in the neuropathology of Alzheimer's disease by forming intracellular neurofibrillary tangles. Tau in the normal physiological condition helps stabilize microtubules and transport. Tau aggregates due to various gene mutations, intracellular insults and abnormal post-translational modifications, phosphorylation being the most important one. Other modifications which alter the function of Tau protein are glycation, nitration, acetylation, methylation, oxidation, etc. In addition to forming intracellular aggregates, Tau pathology might spread in a prion-like manner as revealed by several in vitro and in vivo studies. The possible mechanism of Tau spread can be via bulk endocytosis of misfolded Tau species. The recent studies elucidating this mechanism have mainly focussed on the aggregation and spread of repeat domain of Tau in the cell culture models. Further studies are needed to elucidate the prion-like propagation property of full-length Tau and its aggregates in a more intense manner in vitro as well as in vivo conditions. Varied post-translational modifications can have discrete effects on aggregation propensity of Tau as well as its propagation. Here, we review the prion-like properties of Tau and hypothesize the role of glycation in prion-like properties of Tau. This post-translationally modified Tau might have an enhanced propagation property due to differential properties conferred by the modifications.

10aAlzheimer disease10aPost-translational modifications of tau10aPropagation of tau10aTau10aTauopathies1 aSonawane, Shweta, Kishor1 aChinnathambi, Subashchandrabose uhttp://library.ncl.res.in/content/prion-propagation-post-translationally-modified-tau-alzheimers-disease-hypothesis01800nas a2200265 4500008004100000022001400041245007700055210006900132260000800201300001100209490000800220520092900228653002201157653001401179653002501193653002901218653002401247653001601271100002901287700002801316700002001344700002601364700003601390856010801426 2019 eng d a0003-986100aBaicalein suppresses repeat tau fibrillization by sequestering oligomers0 aBaicalein suppresses repeat tau fibrillization by sequestering o cOCT a1081190 v6753 a

Alzheimer's disease (AD) is a neurodegenerative disorder caused by protein misfolding, aggregation and accumulation in the brain. A large number of molecules are being screened against these pathogenic proteins but the focus for therapeutics is shifting towards the natural compounds as aggregation inhibitors, mainly due to their minimum adverse effects. Baicalein is a natural compound belonging to the class of flavonoids isolated from the Chinese herb Scutellaria baicalensis. Here we applied fluorescence, absorbance, microscopy, MALDI-TOF spectrophotometry and other biochemical techniques to investigate the interaction between Tau and Baicalein in vitro. We found the aggregation inhibitory properties of Baicalein for the repeat Tau. Overall, the potential of Baicalein in dissolving the preformed Tau oligomers as well as mature fibrils can be of utmost importance in therapeutics for Alzheimer's disease.

10aAlzheimer disease10aBaicalein10aMicrotubule assembly10aPaired helical filaments10aProtein aggregation10atau protein1 aSonawane, Shweta, Kishor1 aBalmik, Abhishek, Ankur1 aBoral, Debjyoti1 aRamasamy, Sureshkumar1 aChinnathambi, Subashchandrabose uhttp://library.ncl.res.in/content/baicalein-suppresses-repeat-tau-fibrillization-sequestering-oligomers03031nas a2200337 4500008004100000245018300041210006900224260000800293300001200301490000700313520189600320653002202216653001702238653001402255653002002269653002202289653002302311100001902334700002002353700001702373700001702390700001902407700002402426700001702450700001802467700002602485700001702511700001802528700001602546856013102562 2025 eng d00aIsobavachalcone ameliorates Alzheimer disease pathology by autophagy-mediated clearance of amyloid beta and inhibition of NLRP3 inflammasome in primary astrocytes and 5x-FAD mice0 aIsobavachalcone ameliorates Alzheimer disease pathology by autop cMAR a15253640 v163 a

Background and Aim Alzheimer's disease (AD) progresses with A beta plaque deposition and neuroinflammation. Given the complexity of AD pathology, single-target therapies have frequently failed in clinical trials. We hypothesized that a multitarget approach could yield better therapeutic outcomes. To this end, we identified isobavachalcone (IBC), a natural compound with dual pharmacological activity in reducing A beta plaques and neuroinflammation.Experimental Procedure Primary astrocytes were isolated from 3 to 4 days old C57BL/6J mice pups for in-vitro assays, while in-vivo studies were conducted on 5x-FAD mice. Protein alterations were evaluated using ELISA, western blotting, immunocytochemistry, and immunohistochemistry. Behavioral analyses included the radial arm maze, open field, and rotarod tests. Data from all in vitro and in vivo experiments were analyzed by using one-way ANOVA and post-hoc Bonferroni tests.Results In-vitro analyses in astrocytes demonstrated that IBC at 5 and 10 mu M concentrations induce AMPK phosphorylation through CAMKK2, promoting autophagy and inhibiting the NLRP3 inflammasome in primary astrocytes. IBC-treated astrocytes exhibited significant clearance of extracellular amyloid beta. Mechanistic studies highlighted autophagy as a key factor in reducing both NLRP3 inflammasome activity and A beta levels. Two months of treatment of 5x-FAD mice with IBC at 25 and 50 mg/kg significantly improved cognitive functions, as evidenced by enhanced memory and motor performance in behavioral tests. Subsequent brain tissue analysis revealed that IBC upregulated autophagic proteins to reduce the brain's amyloid beta levels, resulting in decreased expression of neuroinflammation markers.Conclusion IBC effectively ameliorates AD pathology through autophagy-mediated clearance of A beta and suppressing neuroinflammation in 5x-FAD mice.

10aAlzheimer disease10aAmyloid beta10aAutophagy10aisobavachalcone10aneuroinflammation10aNLRP3 inflammasome1 aKour, Dilpreet1 aKhajuria, Parul1 aSharma, Kuhu1 aSharma, Alpa1 aSharma, Ankita1 aAli, Syed, Mudassir1 aWazir, Priya1 aRamajayan, P.1 aSawant, Sanghapal, D.1 aNandi, Utpal1 aAhmed, Zabeer1 aKumar, Ajay uhttp://library.ncl.res.in/content/isobavachalcone-ameliorates-alzheimer-disease-pathology-autophagy-mediated-clearance-amyloid