Abstract
Background: Alzheimer´s disease, a progressive and degenerative disorder of the brain, is the most common cause of dementia among the elderly. To face its multifactorial nature, the use of single compounds that can simultaneously modulate different targets involved in the neurodegenerative cascade has emerged as an interesting therapeutic approach.
Objective: This work investigated the ability of uleine, the major indole alkaloid purified from stem barks of the Brazilian medicinal plant Himatanthus lancifolius, to interact with crucial Alzheimer´s disease disruptive targets associated with two of its major neurodegenerative pathways: acetylcholinesterase and butyrylcholinesterase (cholinergic pathway) and β-secretase and β-amyloid peptide (amyloidogenic pathway). Methods: Uleine’s capacity to inhibit human acetylcholinesterase and butyrylcholinesterase enzymes was determined measuring the difference between reaction rates with and without uleine monitored at 412 nm using 5,5’- dithiobis-(2- nitrobenzoic acid) as colorimetric agent. FRET based assay was used to evaluate β-secretase inhibition using DABCYL- Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-EDANS as substrate and β-amyloid peptide spontaneous aggregation assay was performed using the thioflavin T spectroscopy assay. Cell viability and toxicity experiments with PC12 and SH-SY5Y cell lines were performed using the MTT colorimetric assay. Results: Uleine demonstrated strong inhibitory activities for both cholinesterases (IC50 279.0±4.5 and 24.0±1.5 μM, respectively) and β-secretase (IC50 180±22 nM). Above all, uleine significantly inhibited the self-aggregation of amyloid- β peptide and was not toxic for PC12 or SH-SY5Y neuronal cells. Conclusion: These data show for the first time that the natural compound uleine has a novel, multieffective ability to decelerate or even inhibit the development of Alzheimer´s disease.Keywords: Alzheimer's disease, acetylcholinesterase, butyrylcholinesterase, β-secretase, β-amyloid aggregation, uleine.
Current Alzheimer Research
Title:Uleine Disrupts Key Enzymatic and Non-Enzymatic Biomarkers that Leads to Alzheimer’s Disease
Volume: 14 Issue: 3
Author(s): Claudia Seidl, Cid Aimbire de Moraes Santos, Angela De Simone, Manuela Bartolini, Almeriane Maria Weffort-Santos and Vincenza Andrisano
Affiliation:
Keywords: Alzheimer's disease, acetylcholinesterase, butyrylcholinesterase, β-secretase, β-amyloid aggregation, uleine.
Abstract: Background: Alzheimer´s disease, a progressive and degenerative disorder of the brain, is the most common cause of dementia among the elderly. To face its multifactorial nature, the use of single compounds that can simultaneously modulate different targets involved in the neurodegenerative cascade has emerged as an interesting therapeutic approach.
Objective: This work investigated the ability of uleine, the major indole alkaloid purified from stem barks of the Brazilian medicinal plant Himatanthus lancifolius, to interact with crucial Alzheimer´s disease disruptive targets associated with two of its major neurodegenerative pathways: acetylcholinesterase and butyrylcholinesterase (cholinergic pathway) and β-secretase and β-amyloid peptide (amyloidogenic pathway). Methods: Uleine’s capacity to inhibit human acetylcholinesterase and butyrylcholinesterase enzymes was determined measuring the difference between reaction rates with and without uleine monitored at 412 nm using 5,5’- dithiobis-(2- nitrobenzoic acid) as colorimetric agent. FRET based assay was used to evaluate β-secretase inhibition using DABCYL- Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-EDANS as substrate and β-amyloid peptide spontaneous aggregation assay was performed using the thioflavin T spectroscopy assay. Cell viability and toxicity experiments with PC12 and SH-SY5Y cell lines were performed using the MTT colorimetric assay. Results: Uleine demonstrated strong inhibitory activities for both cholinesterases (IC50 279.0±4.5 and 24.0±1.5 μM, respectively) and β-secretase (IC50 180±22 nM). Above all, uleine significantly inhibited the self-aggregation of amyloid- β peptide and was not toxic for PC12 or SH-SY5Y neuronal cells. Conclusion: These data show for the first time that the natural compound uleine has a novel, multieffective ability to decelerate or even inhibit the development of Alzheimer´s disease.Export Options
About this article
Cite this article as:
Seidl Claudia, Santos Aimbire de Moraes Cid, Simone De Angela, Bartolini Manuela, Weffort-Santos Maria Almeriane and Andrisano Vincenza, Uleine Disrupts Key Enzymatic and Non-Enzymatic Biomarkers that Leads to Alzheimer’s Disease, Current Alzheimer Research 2017; 14 (3) . https://dx.doi.org/10.2174/1567205013666161026150455
DOI https://dx.doi.org/10.2174/1567205013666161026150455 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
Cutting through the Complexities of mTOR for the Treatment of Stroke
Current Neurovascular Research Serotonin 5-HT<sub>1A</sub> Receptors and Antipsychotics - An Update in Light of New Concepts and Drugs
Current Pharmaceutical Design Cognitive Impairment and Diabetes
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Neurobiological Mechanisms of Stress Resilience and Implications for the Aged Population
Current Neuropharmacology Nicotinamide and its Pharmacological Properties for Clinical Therapy
Drug Design Reviews - Online (Discontinued) Genetic Risk Factors in Cerebrovascular Disorders and Cognitive Deterioration
Current Genomics Potential Novel Treatments for Bipolar Depression: Ketamine, Fatty Acids, Anti-inflammatory Agents, and Probiotics
CNS & Neurological Disorders - Drug Targets The Yin and Yang of Antiviral Innate Immunity in Central Nervous System
Current Pharmaceutical Design The Clinical and Biological Relationship between Type II Diabetes Mellitus and Alzheimers Disease
Current Alzheimer Research An Update of the Review of Neuropsychological Consequences of HIV and Substance Abuse: A Literature Review and Implications for Treatment and Future Research
Current Drug Abuse Reviews NAD<sup>+</sup>/NADH Metabolism and NAD<sup>+</sup>-Dependent Enzymes in Cell Death and Ischemic Brain Injury: Current Advances and Therapeutic Implications
Current Medicinal Chemistry Ca2+ Signalling in Damaged Endothelium and Arterial Remodelling: Do Connexin Hemichannels Provide a Suitable Target to Prevent In-stent Restenosis?
Current Drug Therapy The Parietal Atrophy Score on Brain Magnetic Resonance Imaging is a Reliable Visual Scale
Current Alzheimer Research Chemokines and Brain Functions
Current Drug Targets - Inflammation & Allergy Plasma Steroid Level Measured Using Modern Separation Techniques as Biomarkers in Biological Diagnostics
Current Pharmaceutical Analysis Endothelins and the Role of Endothelin Antagonists in the Management of Posttraumatic Vasospasm
Current Pharmaceutical Design Conformation as the Therapeutic Target for Neurodegenerative Diseases
Current Alzheimer Research Safety and Efficacy of Bridging with Low Molecular Weight Heparins: A Systematic Review and Partial Meta-Analysis
Current Pharmaceutical Design Protein Interaction Studies for Understanding the Tremor Pathway in Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets Role of Mitochondrial Protein Quality Control in Oxidative Stress-induced Neurodegenerative Diseases
Current Alzheimer Research