Abstract
α-Synuclein aggregation is centrally implicated in Parkinsons disease (PD). It involves multi-step nucleated polymerization process via the formation of dimers, soluble toxic oligomers and insoluble fibrils. In the present study, we synthesized a novel compound viz., Curcumin-glucoside (Curc-gluc), a modified form of curcumin and studied its anti-aggregating potential with α-synuclein. Under aggregating conditions in vitro, Curc-gluc prevents oligomer formation as well as inhibits fibril formation indicating favorable stoichiometry for inhibition. The binding efficacies of Curc-gluc to both α-synuclein monomeric and oligomeric forms were characterized by micro-calorimetry. It was observed that titration of Curc-gluc with α-synuclein monomer yielded very low heat values with low binding while, in case of oligomers, Curc-gluc showed significant binding. Addition of Curc-gluc inhibited aggregation in a dosedependent manner and enhanced α-synuclein solubility, which propose that Curc-gluc solubilizes the oligomeric form by disintegrating preformed fibrils and this is a novel observation. Overall, the data suggest that Curc-gluc binds to α-synuclein oligomeric form and prevents further fibrillization of α-synuclein; this might aid the development of disease modifying agents in preventing or treating PD.
Keywords: Alpha-synuclein, Parkinson's disease, curcumin-glucoside, oligomer, aggregation, diferulomethane, Thioflavin, Fluorescence, sonication, Tris buffer
Current Pharmaceutical Design
Title: Curcumin-glucoside, A Novel Synthetic Derivative of Curcumin, Inhibits α-Synuclein Oligomer Formation: Relevance to Parkinson's Disease
Volume: 18 Issue: 1
Author(s): Bharathi Shrikanth Gadad, Parvathy K. Subramanya, Srinivas Pullabhatla, Indi S. Shantharam and Rao K.S.
Affiliation:
Keywords: Alpha-synuclein, Parkinson's disease, curcumin-glucoside, oligomer, aggregation, diferulomethane, Thioflavin, Fluorescence, sonication, Tris buffer
Abstract: α-Synuclein aggregation is centrally implicated in Parkinsons disease (PD). It involves multi-step nucleated polymerization process via the formation of dimers, soluble toxic oligomers and insoluble fibrils. In the present study, we synthesized a novel compound viz., Curcumin-glucoside (Curc-gluc), a modified form of curcumin and studied its anti-aggregating potential with α-synuclein. Under aggregating conditions in vitro, Curc-gluc prevents oligomer formation as well as inhibits fibril formation indicating favorable stoichiometry for inhibition. The binding efficacies of Curc-gluc to both α-synuclein monomeric and oligomeric forms were characterized by micro-calorimetry. It was observed that titration of Curc-gluc with α-synuclein monomer yielded very low heat values with low binding while, in case of oligomers, Curc-gluc showed significant binding. Addition of Curc-gluc inhibited aggregation in a dosedependent manner and enhanced α-synuclein solubility, which propose that Curc-gluc solubilizes the oligomeric form by disintegrating preformed fibrils and this is a novel observation. Overall, the data suggest that Curc-gluc binds to α-synuclein oligomeric form and prevents further fibrillization of α-synuclein; this might aid the development of disease modifying agents in preventing or treating PD.
Export Options
About this article
Cite this article as:
Shrikanth Gadad Bharathi, K. Subramanya Parvathy, Pullabhatla Srinivas, S. Shantharam Indi and K.S. Rao, Curcumin-glucoside, A Novel Synthetic Derivative of Curcumin, Inhibits α-Synuclein Oligomer Formation: Relevance to Parkinson's Disease, Current Pharmaceutical Design 2012; 18 (1) . https://dx.doi.org/10.2174/138161212798919093
DOI https://dx.doi.org/10.2174/138161212798919093 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Natural Compounds and Plant Extracts as Therapeutics Against Chronic Inflammation in Alzheimer's Disease - A Translational Perspective
CNS & Neurological Disorders - Drug Targets Preclinical Studies and Clinical Trials with Mesenchymal Stem Cell for Demyelinating Diseases: A Systematic Review
Current Stem Cell Research & Therapy Role of the heme oxygenase-adiponectin-atrial natriuretic peptide axis in renal function
Current Pharmaceutical Design Examination of Hippocampal Differences Between Alzheimer Disease, Amnestic Mild Cognitive Impairment and Normal Aging: Diffusion Kurtosis
Current Alzheimer Research Emerging Concepts in the Analysis of Mitochondrial Genome Instability
Current Genomics Protection and Restitution of Gut Barrier by Probiotics: Nutritional and Clinical Implications
Current Nutrition & Food Science Recent Advances and Approaches in Targeting Apoptosis Signaling Pathways for Anti-Cancer Therapeutics
Current Cancer Therapy Reviews Can Diet and Physical Activity Limit Alzheimer's Disease Risk?
Current Alzheimer Research Potentials of ES Cell Therapy in Neurodegenerative Diseases
Current Pharmaceutical Design Antioxidant Activity of Galantamine and Some of its Derivatives
Current Medicinal Chemistry Kynurenine Pathway and Disease: An Overview
CNS & Neurological Disorders - Drug Targets Cognitive Impairment in Systemic Lupus Erythematosus: Prevalence and Clinical Importance
Current Rheumatology Reviews Cellular and Molecular Mechanisms of Dementia: Decoding the Causal link of Diabetes Mellitus in Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets Immunotherapy in a Rabbit Model of Alzheimer’s Disease
Drug Delivery Letters Pharmacogenetics and Pharmacotherapy of Military Personnel Suffering from Post-traumatic Stress Disorder
Current Neuropharmacology Preclinical Data Supporting/Refuting the Use of Hypericum perforatum in the Treatment of Depression
CNS & Neurological Disorders - Drug Targets Phenotypic Screening Strategies for Neurodegenerative Diseases: A Pathway to Discover Novel Drug Candidates and Potential Disease Targets or Mechanisms
CNS & Neurological Disorders - Drug Targets Sports Medicine Applications of Platelet Rich Plasma
Current Pharmaceutical Biotechnology Diagnosis and Treatment of Alzheimers Disease
Current Medicinal Chemistry - Central Nervous System Agents Neuroprotective Effects of Exercise Treatments After Injury: The Dual Role of Neurotrophic Factors
Current Neuropharmacology