02051nas 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-cells01956nas a2200253   4500008004100000022001400041245007600055210006900131260000900200300001400209490000800223520116500231653001601396653002401412653001101436653001501447653002001462653000801482100002801490700001601518700002501534700003601559856010701595       2020                        eng d  a0141-813000aTransition metal nickel prevents Tau aggregation in Alzheimer's disease0 aTransition metal nickel prevents Tau aggregation in Alzheimers d  cAUG   a1359-13650 v1563 a<p>Alzheimer's disease is the leading cause of dementia, effecting majority of aged people worldwide. The multifaceted effectors of Alzheimer's disease primarily include Tau, amyloid-beta along with hyper activation of kinases, oxidative stress and mutations etc., makes it challenging to design therapeutics. Tau is a microtubule-associating protein, which is subjected to cellular stress resulting in the formation of neurofibrillary tangles, leading to loss of affinity for microtubules. This causes loss of microtubule stability and in turn alters axonal integrity. In the present work, emphasis towards understanding interaction of nickel with Tau was made. Metals such as iron, zinc, copper and lead etc., are known to modulate Tau conformation and enhance its aggregation. Our results showed the deliverance of Tau aggregation by nickel and its synthetic morpholine conjugate. Nickel prevents aggregation by inducing degradation of Tau as evidenced by SDS-PAGE and TEM. Nickel and the synthetic conjugate being non toxic to neuro2a cells and prevent Tau aggregation, might direct these complexes to overcome AD. (C) 2019 Published by Elsevier B.V.</p>
10aAggregation10aAlzheimer's disease10ametals10aMorpholine10aNickel chloride10aTau1 aGorantla, Nalini, Vijay1 aDas, Rashmi1 aBalaraman, Ekambaram1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/transition-metal-nickel-prevents-tau-aggregation-alzheimers-disease