01944nas a2200145   4500008004100000245008100041210006900122300000900191490000900200520139000209100002801599700002501627700003601652856011001688       2017                        eng d00aConformational dynamics of intracellular tau protein revealed by cd and saxs0 aConformational dynamics of intracellular tau protein revealed by  a3-200 v15233 a<p>A native conformation of a protein is essential for its biological role. In certain conditions, some proteins show non-native conformations, leading to aggregation, which in turn may produce severe pathologies. Such physiological conditions are classified as protein misfolding diseases. Alzheimer’s disease (AD) is the most common form of dementia. Extracellular senile plaques formed by Amyloid β and intracellular aggregates formed by microtubule-associated protein Tau (MAPT) are the hallmarks of AD. Physiological role of MAPT is to maintain the integrity and stability of microtubules, however it tends to self-aggregate forming intracellular paired helical filaments (PHFs) during AD. MAPT is also subjected to various post-translational modifications such as phosphorylation, glycosylation, truncation, and acetylation. Being natively unfolded, MAPT is prone to full characterization at atomic level. Small-angle X-ray scattering (SAXS) is often applied in combination with other biophysical methods, like nuclear magnetic resonance (NMR), circular dichroism (CD), fluorescence spectroscopy, analytical ultracentrifugation (AUC), or dynamic light scattering (DLS) to characterize natively unfolded systems. Here we describe the practical aspects of MAPT characterization by SAXS and CD in detail as well as outline the inferred structural and functional implications.</p>1 aGorantla, vijay, nalini1 aAlexander, Shkumatov1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/conformational-dynamics-intracellular-tau-protein-revealed-cd-and-saxs02051nas a2200229   4500008004100000022001400041245009500055210006900150260000900219300001200228490000800240520126000248653002401508653002401532653002001556653001901576653001701595100002101612700002501633700003601658856012701694       2020                        eng d  a0141-813000aCobalt-based metal complexes prevent repeat tau aggregation and nontoxic to neuronal cells0 aCobaltbased metal complexes prevent repeat tau aggregation and n  cJUN   a171-1790 v1523 a<p>Alzheimer's disease (AD) is a fatal neurodegenerative disorder with an alarming increase in the death rate every year. AD is characterised by an aberrant accumulation of proteins in the form of aggregates. The axonal microtubule-associated protein Tau and arnyloid-beta undergo structural transition to beta-sheet rich structure and form aggregates in neuronal soma as well as in the extracellular region. The loss of Tau from microtubules leads to the disintegration of axon and causing neuronal degeneration. This led to the development of effective drugs against AD, to prevent Tau aggregation. Here, we synthesized and screen metal-based complexes to prevent Tau protein aggregation. ThS fluorescence and TEM suggested the role of synthetic cobalt complexes in inhibiting Tau aggregation. CD spectroscopy showed that these complexes prevented conformational changes in Tau to beta-sheet. CBMCs were not toxic at lower concentrations and formed non-toxic Tau species. L1 and L2 prevented membrane leakage: whereas, higher concentrations of L3 caused membrane leakage as observed by LDH release assay. The overall results indicate the synthetic cobalt complexes to be a promising molecule against AD. (C) 2020 Elsevier B.V. All rights reserved.</p>
10aAlzheimer's disease10aCobalt-based metals10aTau Aggregation10aTau inhibition10aTau toxicity1 aGorantla, Nalini1 aBalaraman, Ekambaram1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/cobalt-based-metal-complexes-prevent-repeat-tau-aggregation-and-nontoxic-neuronal-cells