Journal ArticleDOI
Polyphenolic flavonoid (Myricetin) upregulated proteasomal degradation mechanisms: Eliminates neurodegenerative proteins aggregation.
Vibhuti Joshi,Ribhav Mishra,Arun Upadhyay,Ayeman Amanullah,Krishna Mohan Poluri,Sarika Singh,Amit Kumar,Amit Mishra +7 more
TLDR
It is shown that Myricetin, a flavonoid, can eliminate various abnormal proteins from the cellular environment via modulating endogenous levels of Hsp70 chaperone and quality control (QC)‐E3 ubiquitin ligase E6‐AP and reduce the misfolded proteins inclusions, which further alleviates cytotoxicity.Abstract:
Major neurodegenerative disorders are characterized by the formation of misfolded proteins aggregates inside or outside the neuronal cells. Previous studies suggest that aberrant proteins aggregates play a critical role in protein homeostasis imbalance and failure of protein quality control (PQC) mechanism, leading to disease conditions. However, we still do not understand the precise mechanisms of PQC failure and cellular dysfunctions associated with neurodegenerative diseases caused by the accumulation of protein aggregates. Here, we show that Myricetin, a flavonoid, can eliminate various abnormal proteins from the cellular environment via modulating endogenous levels of Hsp70 chaperone and quality control (QC)-E3 ubiquitin ligase E6-AP. We have observed that Myricetin treatment suppresses the aggregation of different aberrant proteins. Myricetin also enhances the elimination of various toxic neurodegenerative diseases associated proteins from the cells, which could be reversed by the addition of putative proteasome inhibitor (MG132). Remarkably, Myricetin can also stabilize E6-AP and reduce the misfolded proteins inclusions, which further alleviates cytotoxicity. Taken together these findings suggested that new mechanistic and therapeutic insights based on small molecules mediated regulation of disturbed protein quality control mechanism, which may result in the maintenance of the state of proteostasis.read more
Citations
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Chemical and biological approaches synergize to ameliorate protein-folding diseases
TL;DR: It is demonstrated that the innate cellular protein homeostasis capacity can be enhanced to fold mutated enzymes that would otherwise misfold and be degraded, using small molecule proteostasis regulators.
Journal ArticleDOI
Myricetin bioactive effects: moving from preclinical evidence to potential clinical applications.
Yasaman Taheri,Hafiz Ansar Rasul Suleria,Natália Martins,Oksana Sytar,Oksana Sytar,Ahmet Beyatli,Balakyz Yeskaliyeva,G. A. Seitimova,Bahare Salehi,Prabhakar Semwal,Sakshi Painuli,Anuj Kumar,Elena Azzini,Miquel Martorell,William N. Setzer,Alfred Maroyi,Javad Sharifi-Rad +16 more
TL;DR: New insights are provided on myricetin preclinical pharmacological activities, and role in selected clinical trials, which provide new insights on the neuroprotective activity of this flavonoid.
Introduction To Flavonoids
TL;DR: The introduction to flavonoids is universally compatible with any devices to read and is available in the book collection an online access to it is set as public so you can download it instantly.
Journal ArticleDOI
Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury.
TL;DR: The neuroprotective mechanisms of HSP70 are summarized and potential ways in which this endogenous therapeutic molecule could be practically induced by pharmacological means to ultimately improve neurological outcomes in acute neurological disease are discussed.
Journal ArticleDOI
Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders.
TL;DR: In this paper, a review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease(HD).
References
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Journal ArticleDOI
UCSF Chimera--a visualization system for exploratory research and analysis.
Eric F. Pettersen,Thomas D. Goddard,Conrad C. Huang,Gregory S. Couch,Daniel M. Greenblatt,Elaine C. Meng,Thomas E. Ferrin +6 more
TL;DR: Two unusual extensions are presented: Multiscale, which adds the ability to visualize large‐scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales.
Journal ArticleDOI
AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading
Oleg Trott,Arthur J. Olson +1 more
TL;DR: AutoDock Vina achieves an approximately two orders of magnitude speed‐up compared with the molecular docking software previously developed in the lab, while also significantly improving the accuracy of the binding mode predictions, judging by tests on the training set used in AutoDock 4 development.
Journal ArticleDOI
Chemistry and Biological Activities of Flavonoids: An Overview
Shashank Kumar,Abhay K. Pandey +1 more
TL;DR: The structural features of flavonoids, their beneficial roles in human health, and significance in plants as well as their microbial production are highlighted.
Journal ArticleDOI
Molecular chaperones in protein folding and proteostasis
TL;DR: It is suggested that an age-related decline in proteostasis capacity allows the manifestation of various protein-aggregation diseases, including Alzheimer's disease and Parkinson's disease, which may spring from a detailed understanding of the pathways underlying proteome maintenance.
Journal ArticleDOI
The biochemistry and medical significance of the flavonoids.
TL;DR: Flavonoids are plant pigments that are synthesised from phenylalanine, generally display marvelous colors known from flower petals, mostly emit brilliant fluorescence when they are excited by UV light, and are ubiquitous to green plant cells.
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