Abstract
The currently available experimental data supports the hypothesis that the neuroprotective effect of dimebon is related to the protection of the brain-mitochondria from neurodegeneration. In this study, the influence of dimebon on mitochondria was investigated to gain a better understanding of the neuroprotective effects of this drug. Here, we demonstrate that dimebon enhances the resistance of the isolated rat brain and liver mitochondria to the induction of mitochondrial permeability transition (MPT) by calcium ions even in the presence of atractyloside, a MPT pore (MPTP) opener, but is ineffective against atractyloside-induced mitochondria swelling. Unlike cyclosporine A (CsA), a MPTP inhibitor, Dimebon does not influence the adenine nucleotide translocase (ANT) conformational changes and is not able to prevent the MPT of de-energized mitochondria. Using three different assays, and using amyloid-β peptide for inducing mitochondrial toxicity, we show that the influence of dimebon on the calcium retention capacity (CRC) of mitochondria depends on the mode of calcium addition. No obvious influence of dimebon on CRC was observed under the conditions of calcium infusion in the pump mode but the increase of CRC of rat brain mitochondria was observed when calcium was added in the bolus mode; the addition of calcium in the single pulse mode led to the increase of the lag period of calcium efflux from mitochondria. From these studies it is shown that dimebon is effective against amyloid-β (Aβ) potentiated mitochondrial swelling and decrease of calcium retention capacity (CRC) of the brain mitochondria.
Keywords: Alzheimer disease, brain and liver mitochondria, calcium retention capacity, dimebon, mitochondrial permeability transition (MPT).
Current Alzheimer Research
Title:Dimebon Attenuates the Aβ-Induced Mitochondrial Permeabilization
Volume: 11 Issue: 5
Author(s): Elena F. Shevtsova, Daria V. Vinogradova, Elena G. Kireeva, V. Prakash Reddy, Gjumrakch Aliev and Sergey O.Bachurin
Affiliation:
Keywords: Alzheimer disease, brain and liver mitochondria, calcium retention capacity, dimebon, mitochondrial permeability transition (MPT).
Abstract: The currently available experimental data supports the hypothesis that the neuroprotective effect of dimebon is related to the protection of the brain-mitochondria from neurodegeneration. In this study, the influence of dimebon on mitochondria was investigated to gain a better understanding of the neuroprotective effects of this drug. Here, we demonstrate that dimebon enhances the resistance of the isolated rat brain and liver mitochondria to the induction of mitochondrial permeability transition (MPT) by calcium ions even in the presence of atractyloside, a MPT pore (MPTP) opener, but is ineffective against atractyloside-induced mitochondria swelling. Unlike cyclosporine A (CsA), a MPTP inhibitor, Dimebon does not influence the adenine nucleotide translocase (ANT) conformational changes and is not able to prevent the MPT of de-energized mitochondria. Using three different assays, and using amyloid-β peptide for inducing mitochondrial toxicity, we show that the influence of dimebon on the calcium retention capacity (CRC) of mitochondria depends on the mode of calcium addition. No obvious influence of dimebon on CRC was observed under the conditions of calcium infusion in the pump mode but the increase of CRC of rat brain mitochondria was observed when calcium was added in the bolus mode; the addition of calcium in the single pulse mode led to the increase of the lag period of calcium efflux from mitochondria. From these studies it is shown that dimebon is effective against amyloid-β (Aβ) potentiated mitochondrial swelling and decrease of calcium retention capacity (CRC) of the brain mitochondria.
Export Options
About this article
Cite this article as:
Shevtsova F. Elena, Vinogradova V. Daria, Kireeva G. Elena, Reddy Prakash V., Aliev Gjumrakch and O.Bachurin Sergey, Dimebon Attenuates the Aβ-Induced Mitochondrial Permeabilization, Current Alzheimer Research 2014; 11 (5) . https://dx.doi.org/10.2174/1567205011666140505094808
DOI https://dx.doi.org/10.2174/1567205011666140505094808 |
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
-
Iron Chelators as Anti-Neoplastic Agents: Current Developments and Promise of the PIH Class of Chelators
Current Medicinal Chemistry Glycoconjugates in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Bcl-2 Inhibitors: Emerging Drugs in Cancer Therapy
Current Medicinal Chemistry Genetic Variants in Genes Involved in Mechanisms of Chemoresistance to Anticancer Drugs
Current Cancer Drug Targets Suicide Gene Therapy Mediated by the Herpes Simplex Virus Thymidine Kinase Gene / Ganciclovir System: Fifteen Years of Application
Current Gene Therapy Characterization of Pharmaceutical IgG and Biosimilars Using Miniaturized Platforms and LC-MS/MS
Current Pharmaceutical Biotechnology The Chemistry and Pharmacology of Genistein
The Natural Products Journal Association of Metronidazole with Cancer: A Potential Risk Factor or Inconsistent Deductions?
Current Drug Metabolism Status of Flavonols as P-Glycoprotein Inhibitors in Cancer Chemotherapy
Current Cancer Therapy Reviews Metastasis Suppressors: Basic and Translational Advances
Current Pharmaceutical Biotechnology Possible Neuroprotective Strategies in ALS
Current Neuropharmacology Recent Progress of Src Family Kinase Inhibitors as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Induced Pluripotent Stem Cell-Based Studies of Parkinson's Disease: Challenges and Promises
CNS & Neurological Disorders - Drug Targets Exosomes: The Messengers of Health and Disease
Current Neuropharmacology Parkinson’s Disease and Alpha-Synucleinopathies: from Arising Pathways to Therapeutic Challenge
Central Nervous System Agents in Medicinal Chemistry Novel Natural and Synthetic Ligands of the Endocannabinoid System
Current Medicinal Chemistry Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment
Current Cancer Drug Targets Neuroglobin and Estrogen Receptors: A New Pathway of Cell Survival and Cell Death Balance
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Cellular Senescence in the Development and Treatment of Cancer
Current Pharmaceutical Design Microtubules in Apoptosis Induction: Are They Necessary?
Current Cancer Drug Targets