Basic Limonoid modulates Chaperone-mediated Proteostasis and dissolve Tau fibrils.

Scientific Reports
Nalini V GorantlaSubashchandrabose Chinnathambi

Abstract

The Alzheimer's disease pathology is associated with accumulation of intracellular neurofibrillary tangles and extracellular senile plaques. The formation of initial nucleus triggers conformational changes in Tau and leads to its deposition. Hence, there is a need to eliminate these toxic proteins for proper functioning of neuronal cells. In this aspect, we screened the effect of basic limonoids such as gedunin, epoxyazadiradione, azadirone and azadiradione on inhibiting Tau aggregation as well as disintegration of induced Tau aggregates. It was observed that these basic limonoids effectively prevented aggregates formation by Tau and also exhibited the property of destabilizing matured Tau aggregates. The molecular docking analysis suggests that the basic limonoids interact with hexapeptide regions of aggregated Tau. Although these limonoids caused the conformational changes in Tau to β-sheet structure, the cytological studies indicate that basic limonoids rescued cell death. The dual role of limonoids in Tau aggregation inhibition and disintegration of matured aggregates suggests them to be potent molecules in overcoming Tau pathology. Further, their origin from a medicinally important plant neem, which known to possess remark...Continue Reading

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Citations

Sep 8, 2020·Apoptosis : an International Journal on Programmed Cell Death·Vipin RaiSubash C Gupta
Sep 19, 2020·Cell & Bioscience·Hariharakrishnan ChidambaramSubashchandrabose Chinnathambi
Jul 12, 2020·Journal of Alzheimer's Disease : JAD·Camila CalfioRicardo B Maccioni
Dec 16, 2020·Journal of Biomolecular Structure & Dynamics·Hariharakrishnan Chidambaram, Subashchandrabose Chinnathambi
Mar 24, 2021·Neurochemistry International·Rajat SandhirNitin Kumar Singhal

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Methods Mentioned

BETA
size-exclusion chromatography
fluorescence assay
Electrophoresis
filter trap assay
Assay
the nuclear

Software Mentioned

AutoDock Tools
AutoGrid4
PyMol
LigPlot
Systat
Autodock4
OpenBabel
Zen
Gaussian
GalaxyWEB

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