High-affinity binding of celastrol to monomeric ?-synuclein mitigates invitro aggregation
- Title
- High-affinity binding of celastrol to monomeric ?-synuclein mitigates invitro aggregation
- Creator
- Kavya R.; Aouti S.; Jos S.; Prasad T.K.; Kumuda K.N.; Unni S.; Padmanabhan B.; Kamariah N.; Padavattan S.; Mythri R.B.
- Description
- ?-Synuclein (?Syn) aggregation is associated with Parkinsons disease (PD). The region ?Syn36-42 acts as the nucleation 'master controller and ?Syn1-12 as a secondary nucleation site. They drive monomeric ?Syn to aggregation. Small molecules targeting these motifs are promising for disease-modifying therapy. Using computational techniques, we screened thirty phytochemicals for ?Syn binding. The top three compounds were experimentally validated for their binding affinity. Amongst them, celastrol showed high binding affinity. NMR analysis confirmed stable ?Syn-celastrol interactions involving several residues in the N-terminus and NAC regions but not in the C-terminal tail. Importantly, celastrol interacted extensively with the key motifs that drive ?Syn aggregation. Thioflavin-T assay indicated that celastrol reduced ?Syn aggregation. Thus, celastrol holds promise as a potent drug candidate for PD. Communicated by Ramaswamy H. Sarma. 2023 Informa UK Limited, trading as Taylor & Francis Group.
- Source
- Journal of Biomolecular Structure and Dynamics, Vol-41, No. 22, pp. 12703-12713.
- Date
- 2023-01-01
- Publisher
- Taylor and Francis Ltd.
- Subject
- aggregation; celastrol; Parkinsons disease; phytochemical; ?-Synuclein
- Coverage
- Kavya R., Department of Biotechnology, Mount Carmel College, Autonomous, Karnataka, Bengaluru, India; Aouti S., Department of Biophysics, National Institute of Mental Health and Neurosciences, Karnataka, Bengaluru, India; Jos S., Department of Biophysics, National Institute of Mental Health and Neurosciences, Karnataka, Bengaluru, India; Prasad T.K., Centre for Chemical Biology & Therapeutics, Institute for Stem Cell Science and Regenerative Medicine, Karnataka, Bengaluru, India; Kumuda K.N., Department of Biotechnology, Mount Carmel College, Autonomous, Karnataka, Bengaluru, India, Department of Biosciences, School of science and technology, Nottingham Trent University, Clifton Campus, Clifton Ln, Clifton, Nottingham, NG11 8NS, United Kingdom; Unni S., Department of Biophysics, National Institute of Mental Health and Neurosciences, Karnataka, Bengaluru, India, European Molecular Biology Laboratory, EMBL, 71, Avenue des Martyrs, CS 90181, Cedex 9, Grenoble, 34042, France; Padmanabhan B., Department of Biophysics, National Institute of Mental Health and Neurosciences, Karnataka, Bengaluru, India; Kamariah N., Centre for Chemical Biology & Therapeutics, Institute for Stem Cell Science and Regenerative Medicine, Karnataka, Bengaluru, India; Padavattan S., Department of Biophysics, National Institute of Mental Health and Neurosciences, Karnataka, Bengaluru, India; Mythri R.B., Department of Biotechnology, Mount Carmel College, Autonomous, Karnataka, Bengaluru, India, Department of Psychology, Christ (Deemed to be University), Dharmaram College Post, Hosur Road, Karnataka, Bengaluru, 560029, India
- Rights
- Restricted Access
- Relation
- ISSN: 7391102; PubMed ID: 36744543; CODEN: JBSDD
- Format
- Online
- Language
- English
- Type
- Article
Collection
Citation
Kavya R.; Aouti S.; Jos S.; Prasad T.K.; Kumuda K.N.; Unni S.; Padmanabhan B.; Kamariah N.; Padavattan S.; Mythri R.B., “High-affinity binding of celastrol to monomeric ?-synuclein mitigates invitro aggregation,” CHRIST (Deemed To Be University) Institutional Repository, accessed April 18, 2025, https://archives.christuniversity.in/items/show/14648.