Abstract
Oxidative stress and mitochondrial disturbances are the common and important causative factors of aging, and play an important role in the late onset of sporadic neurodegenerative diseases, including Alzheimer disease (AD). Furthermore, emerging evidence from in vitro and in vivo disease models suggests that oxidative stress and increased vulnerability to induction of mitochondrial permeability transition leads to the pathogenesis of the neurological disorders. Towards the goals of developing effective neuroprotectors, this article describes the synthesis and neuroprotective studies of various derivatives of the naturally occurring alkaloid securinine, based on which a lead compound, allomargaritarine (a diastereomer of margaritarine), was identified as an effective therapeutic for neuroprotection. Allomargaritarine exhibits high antioxidant activity, and has significant mitoprotective effect on cellular models of neurodegeneration.
Keywords: Neurodegenerative diseases, neuroprotection, mitochondria, lipid peroxidation, antioxidant, alkaloids, lactones.
CNS & Neurological Disorders - Drug Targets
Title:Neuroprotective effects of the securinine-analogues: identification of Allomargaritarine as a lead compound
Volume: 15 Issue: 1
Author(s): Margarita E. Neganova, Sergei G. Klochkov, Svetlana V. Afanasieva, Tatiana P. Serkova, Ekaterina S. Chudinova, Sergei O. Bachurin, V. Prakash Reddy, Gjumrakch Aliev and Elena F. Shevtsova
Affiliation:
Keywords: Neurodegenerative diseases, neuroprotection, mitochondria, lipid peroxidation, antioxidant, alkaloids, lactones.
Abstract: Oxidative stress and mitochondrial disturbances are the common and important causative factors of aging, and play an important role in the late onset of sporadic neurodegenerative diseases, including Alzheimer disease (AD). Furthermore, emerging evidence from in vitro and in vivo disease models suggests that oxidative stress and increased vulnerability to induction of mitochondrial permeability transition leads to the pathogenesis of the neurological disorders. Towards the goals of developing effective neuroprotectors, this article describes the synthesis and neuroprotective studies of various derivatives of the naturally occurring alkaloid securinine, based on which a lead compound, allomargaritarine (a diastereomer of margaritarine), was identified as an effective therapeutic for neuroprotection. Allomargaritarine exhibits high antioxidant activity, and has significant mitoprotective effect on cellular models of neurodegeneration.
Export Options
About this article
Cite this article as:
Neganova E. Margarita, Klochkov G. Sergei, Afanasieva V. Svetlana, Serkova P. Tatiana, Chudinova S. Ekaterina, Bachurin O. Sergei, Reddy Prakash V., Aliev Gjumrakch and Shevtsova F. Elena, Neuroprotective effects of the securinine-analogues: identification of Allomargaritarine as a lead compound, CNS & Neurological Disorders - Drug Targets 2016; 15 (1) . https://dx.doi.org/10.2174/1871527314666150821111812
DOI https://dx.doi.org/10.2174/1871527314666150821111812 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Heart and Brain Axis Targets in CNS Neurological Disorders
Recently there has been a surge of interest in delving deeper into the complex interplay between the heart and brain. This fascination stems from a growing recognition of the profound influence each organ holds over the other, particularly in the realm of central nervous system (CNS) neurological disorders. The purpose ...read more
Lifestyle Interventions to Prevent and Treat Cognitive Impairment and Dementia
More than 55 million people live with dementia worldwide. By 2050, the population affected by dementia will exceed 139 million individuals. Mild cognitive impairment (MCI) is a pre-dementia stage, also known as prodromal dementia, affecting older adults. MCI emerges years before the manifestation of dementia but can be avoidable and ...read more
Pathogenic Proteins in Neurodegenerative Diseases: From Mechanisms to Treatment Modalities
The primary objective of this thematic issue is to elucidate the molecular mechanisms by which pathogenic proteins contribute to neurodegenerative diseases and to highlight current and emerging therapeutic strategies aimed at mitigating their effects. By bringing together cutting-edge research and reviews, this issue aims to: 1.Enhance Understanding: Provide a comprehensive ...read more
Role of glial cells in autism spectrum disorder: Molecular mechanism and therapeutic approaches
Emerging evidence suggests that glial cells may play a pivotal role in neuroanatomical and behavioral changes found in autism spectrum disorder (ASD). Many individuals with ASD experience a neuro-immune system abnormalities throughout life, which implicates a potential role of microglia in the pathogenesis of ASD. Dysfunctional astrocytes and oligodendrocytes were ...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
Related Articles
-
Porphyromonas gingivalis Mediated Periodontal Disease and Atherosclerosis:Disparate Diseases with Commonalities in Pathogenesis Through TLRs
Current Pharmaceutical Design Association of Apolipoprotein E (ApoE) Polymorphism with Alzheimer's Disease in Chinese Population
Current Alzheimer Research Genetics and Gene Therapy of Anderson-Fabry Disease
Current Gene Therapy Type 2 Diabetes and Risk for Functional Decline and Disability in Older Persons
Current Diabetes Reviews The GSTM1 and GSTT1 Null Genotypes Increase the Risk for Type 2 Diabetes Mellitus and the Subsequent Development of Diabetic Complications: A Meta-analysis
Current Diabetes Reviews Near Infrared Optical Technologies to Illuminate the Status of the Neonatal Brain
Current Pediatric Reviews Current Concepts on Selected Plant Secondary Metabolites With Promising Inhibitory Effects Against Enzymes Linked to Alzheimer’s Disease
Current Medicinal Chemistry Systemic Adverse Drug Reactions Secondary to Anti-VEGF Intravitreal Injection in Patients with Neovascular Age-Related Macular Degeneration
Current Vascular Pharmacology Visualising Neuroinflammation in Post-Stroke Patients: A Comparative PET Study with the TSPO Molecular Imaging Biomarkers [<sup>11</sup>C]PK11195 and [<sup>11</sup>C]vinpocetine
Current Radiopharmaceuticals Risk Factors for Cardiovascular Disease in Psoriasis: Relation to Inflammation Assessed by the Severity and Duration of Illness
Inflammation & Allergy - Drug Targets (Discontinued) Targeted Vascular Drug Delivery in Cerebral Cancer
Current Pharmaceutical Design Fish Oil Supplementation: A Matter of DHA Enzymatic/Non-Enzymatic Oxidation Balance?
Current Nutrition & Food Science Investigating the Influence of Gut Microbiota-related Metabolites in Gastrointestinal Cancer
Current Cancer Drug Targets Anti-Aggregating Antibodies, a New Approach Towards Treatment of Conformational Diseases
Current Medicinal Chemistry Pharmacologic Targeting of Endothelial Progenitor Cells
Cardiovascular & Hematological Disorders-Drug Targets Effects and Perspectives of Chinese Patent Medicines for Tonifying <i>Qi</i> and Promoting Blood Circulation on Patients with Cerebral Infarction
Current Vascular Pharmacology Anti-Acetylcholinesterase Derivatives: A Privileged Structural Framework in Drug Discovery to Treat Alzheimer’s Disease
Current Enzyme Inhibition How to Get from Here to There: Macrophage Recruitment in Alzheimers Disease
Current Alzheimer Research Association Between Atrophy of the Caudate Nuclei, Global Brain Atrophy, Cerebral Small Vessel Disease and Mild Parkinsonian Signs in Neurologically and Cognitively Healthy Subjects Aged 45-84 Years: A Crosssectional Study
Current Alzheimer Research Oral Antidiabetic Agents: Anti-Atherosclerotic Properties Beyond Glucose Lowering?
Current Pharmaceutical Design