@article {46843, title = {Cobalt-based metal complexes prevent repeat tau aggregation and nontoxic to neuronal cells}, journal = {International Journal of Biological Macromolecules}, volume = {152}, year = {2020}, month = {JUN }, pages = {171-179}, type = {Article}, abstract = {

Alzheimer{\textquoteright}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.

}, keywords = {Alzheimer{\textquoteright}s disease, Cobalt-based metals, Tau Aggregation, Tau inhibition, Tau toxicity}, issn = {0141-8130}, doi = {10.1016/j.ijbiomac.2020.02.278}, author = {Gorantla, V. Nalini and Balaraman, Ekambaram and Chinnathambi, Subashchandrabose} } @article {46609, title = {Role of cysteines in accelerating Tau filament formation}, journal = {Journal of Biomolecular Structure \& Dynamics}, volume = {40}, year = {2022}, month = {JUN}, pages = {4366-4375}, type = {Article}, abstract = {

Alzheimer{\textquoteright}s disease is majorly associated with intracellular accumulation of Tau into paired helical filaments and tangles. The self-aggregated dimeric and oligomeric species of Tau formed are more toxic to neuronal cells and acts as seeds for filament formation. The two cysteine residues and the two hexapeptide regions of full-length Tau play a key role in initialization and filament formation during Tau aggregation. The role of cysteine residues in Tau aggregation has been studied by in-vitro aggregation assay that was measured by Thioflavin S fluorescence to observe the kinetics of aggregation. In this study, we have performed in-vitro aggregation assay with recombinant full-length Tau and the cysteine mutants to understand the mechanism of cysteine independent Tau aggregation. Here, we report that cysteine mutant full-length Tau can aggregate to form filaments under in-vitro conditions. To visualize the polymorphisms of Tau and cysteine mutants under different aggregation conditions anionic cofactor, heparin was employed. Wild-type Tau showed rapid aggregation to form oligomers and filaments. On the other hand, the cysteine mutant delayed the initial Tau aggregation. This indicates the importance of cysteine residues in accelerating initial Tau nucleation for its aggregation. The filament morphology of wild-type and cysteine mutant Tau has been characterized using transmission electron microscopy and high-resolution transmission electron microscopy. Communicated by Ramaswamy H. Sarma

}, keywords = {Heparin-induced aggregation, Paired helical filaments, Tau Aggregation, Tau Oligomers, tau protein}, issn = {0739-1102}, doi = {10.1080/07391102.2020.1856720}, author = {Chidambaram, Hariharakrishnan and Chinnathambi, Subashchandrabose} } @article {48804, title = {Bacopa monnieri reduces Tau aggregation and Tau-mediated toxicity in cells}, journal = {International Journal of Biological Macromolecules}, volume = {234}, year = {2023}, month = {APR}, pages = {123171}, type = {Article}, abstract = {

Alzheimer{\textquoteright}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{\textquoteright}s disease.

}, keywords = {Bacopa monnieri, GSK-3 beta, Nrf2, Nuclear transport, NUP358, Tau Aggregation, Tau phosphorylation}, issn = {0141-8130}, doi = {10.1016/j.ijbiomac.2023.123171}, author = {Dubey, Tushar and Kushwaha, Preeti and Thulasiram, H. V. and Chandrashekar, Madhura and Chinnathambi, Subashchandrabose} }